{"entity": "researcher", "timestamp": "2026-05-15T01:14:29.110Z", "family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "affiliations": ["Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a"}}, "publications": [{"entity": "publication", "iuid": "815f3d67b39942bda4ef5dce0da35f32", "links": {"self": {"href": "https://publications.scilifelab.se/publication/815f3d67b39942bda4ef5dce0da35f32.json"}, "display": {"href": "https://publications.scilifelab.se/publication/815f3d67b39942bda4ef5dce0da35f32"}}, "title": "Lipid\u2010Facilitated Opening of the ADAM10 Sheddase Revealed by Enhanced Sampling Simulations", "authors": [{"family": "Schahl", "given": "Adrien", "initials": "A", "orcid": "0000-0001-5839-7715", "researcher": {"href": "https://publications.scilifelab.se/researcher/91c1503f32d64435a8df615d167a5c6f.json"}}, {"family": "Haloi", "given": "Nandan", "initials": "N", "orcid": "0000-0003-3542-333X", "researcher": {"href": "https://publications.scilifelab.se/researcher/26d4c3c8db3b441994180b93bc6eda98.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Zhang", "given": "Shengpan", "initials": "S"}, {"family": "Sattentau", "given": "Quentin James", "initials": "QJ", "orcid": "0000-0001-7170-1937", "researcher": {"href": "https://publications.scilifelab.se/researcher/d78243e447114e179d1aef437cb35717.json"}}, {"family": "Sezgin", "given": "Erdinc", "initials": "E", "orcid": "0000-0002-4915-388X", "researcher": {"href": "https://publications.scilifelab.se/researcher/34d3b05d68d64f698ff08dc655d2fe26.json"}}, {"family": "Delemotte", "given": "Lucie", "initials": "L", "orcid": "0000-0002-0828-3899", "researcher": {"href": "https://publications.scilifelab.se/researcher/2919e3b5cf0f466f980df8fd700bc306.json"}}, {"family": "Howard", "given": "Rebecca J", "initials": "RJ"}], "type": "journal-article", "published": "2026-02-24", "journal": {"title": "Adv Sci (Weinh)", "issn": "2198-3844", "pages": "e15713", "issn-l": null}, "abstract": "ADAM10 is a crucial membrane-bound metalloprotease that regulates cellular physiology by cleaving and releasing membrane-anchored proteins, including adhesion molecules and growth factor precursors, thereby modulating cell signaling, adhesion, and migration. Despite its central role, its activation mechanisms are not fully understood. Here, we model how phosphatidylserine (PS) exposure during apoptosis triggers ADAM10 activation. We confirm that PS externalization is associated with ADAM10-mediated CD43 shedding from the surface of T cells. Intriguingly, ADAM10 activation correlated with loss of ADAM10 monoclonal antibody binding, suggesting a PS-induced conformational change that alters epitope accessibility. To explore this lipid-mediated conformational change of ADAM10, we employed molecular dynamics simulations to map its conformational landscape. Our simulations revealed that in the absence of PS, ADAM10 samples predominantly closed and intermediate states. By contrast, the presence of PS destabilizes the closed conformation, thereby favoring open states. We provide a mechanistic explanation for this PS-induced conformational change, which drives ADAM10 activation and loss of mAb binding through conformational change. These findings offer new insights into the lipid-mediated regulation of ADAM10 and its conformational dynamics.", "doi": "10.1002/advs.202515713", "pmid": "41733033", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [], "notes": [], "created": "2026-02-25T19:59:11.014Z", "modified": "2026-03-24T09:09:06.921Z"}, {"entity": "publication", "iuid": "1c5a6133d47f4a73ae56d921da61b6df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1c5a6133d47f4a73ae56d921da61b6df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1c5a6133d47f4a73ae56d921da61b6df"}}, "title": "Development of DARPin T cell engagers for specific targeting of tumor-associated HLA/peptide complexes", "authors": [{"family": "Venetz-Arenas", "given": "Natalia", "initials": "N"}, {"family": "Schulte", "given": "Tim", "initials": "T"}, {"family": "M\u00fcller", "given": "Sandra", "initials": "S"}, {"family": "Wallden", "given": "Karin", "initials": "K"}, {"family": "Fischer", "given": "Stefanie", "initials": "S"}, {"family": "Resink", "given": "Tom", "initials": "T"}, {"family": "Kadri", "given": "Nadir", "initials": "N", "orcid": "0000-0003-2623-4094", "researcher": {"href": "https://publications.scilifelab.se/researcher/70724b181f324c7aac42468a177dcff4.json"}}, {"family": "Paladino", "given": "Maria", "initials": "M"}, {"family": "Pina", "given": "Nicole", "initials": "N"}, {"family": "Radom", "given": "Filip", "initials": "F"}, {"family": "Villemagne", "given": "Denis", "initials": "D"}, {"family": "Bruckmaier", "given": "Sandra", "initials": "S"}, {"family": "Cornelius", "given": "Andreas", "initials": "A"}, {"family": "Hospodarsch", "given": "Tanja", "initials": "T"}, {"family": "Alici", "given": "Evren", "initials": "E", "orcid": "0000-0001-5307-6648", "researcher": {"href": "https://publications.scilifelab.se/researcher/94af705a738741dd928e90fe403b9475.json"}}, {"family": "Ljunggren", "given": "Hans Gustaf", "initials": "HG", "orcid": "0000-0003-0908-7387", "researcher": {"href": "https://publications.scilifelab.se/researcher/54d696167bca4a389807143f84baeafe.json"}}, {"family": "Chambers", "given": "Benedict J", "initials": "BJ", "orcid": "0000-0003-0437-8441", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bdd56cf648f4411945163135f9a7140.json"}}, {"family": "Han", "given": "Xiao", "initials": "X"}, {"family": "Sun", "given": "Renhua", "initials": "R", "orcid": "0000-0002-8203-4946", "researcher": {"href": "https://publications.scilifelab.se/researcher/f639c1a9dca647c0b583ce74ab398f02.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Levitsky", "given": "Victor", "initials": "V"}, {"family": "Sandalova", "given": "Tatyana", "initials": "T", "orcid": "0000-0002-7694-6420", "researcher": {"href": "https://publications.scilifelab.se/researcher/8adca17a49fc47b696cb2b2795f83e6f.json"}}, {"family": "Walser", "given": "Marcel", "initials": "M"}, {"family": "Achour", "given": "Adnane", "initials": "A", "orcid": "0000-0003-0432-710X", "researcher": {"href": "https://publications.scilifelab.se/researcher/39682601d1a24f5ba1d103bf74c9acbd.json"}}], "type": "journal-article", "published": "2025-12-00", "journal": {"title": "iScience", "issn": "2589-0042", "volume": "28", "issue": "12", "pages": "113926", "issn-l": "2589-0042"}, "abstract": null, "doi": "10.1016/j.isci.2025.113926", "pmid": null, "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [], "notes": [], "created": "2025-11-23T22:19:59.150Z", "modified": "2025-12-21T19:10:20.517Z"}, {"entity": "publication", "iuid": "73fee7c76bfd49a6944ca090feb04ef1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/73fee7c76bfd49a6944ca090feb04ef1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/73fee7c76bfd49a6944ca090feb04ef1"}}, "title": "Structure of the central Staphylococcus aureus AAA+ protease MecA/ClpC/ClpP.", "authors": [{"family": "Azinas", "given": "Stavros", "initials": "S", "orcid": "0000-0002-3744-9229", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4ec0cb5b5df4b4f89780ce3a08efc89.json"}}, {"family": "Wallden", "given": "Karin", "initials": "K"}, {"family": "Katikaridis", "given": "Panagiotis", "initials": "P"}, {"family": "Jenne", "given": "Timo", "initials": "T", "orcid": "0009-0001-2033-5102", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a27284b457b4d84b7104cfc0a3d989c.json"}}, {"family": "Schahl", "given": "Adrien", "initials": "A", "orcid": "0000-0001-5839-7715", "researcher": {"href": "https://publications.scilifelab.se/researcher/91c1503f32d64435a8df615d167a5c6f.json"}}, {"family": "Mogk", "given": "Axel", "initials": "A", "orcid": "0000-0003-3674-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/56a1d7fc519743029c9ae615086d8093.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}], "type": "journal article", "published": "2025-10-14", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "8", "issue": "1", "pages": "1467", "issn-l": "2399-3642"}, "abstract": "Bacterial AAA+ proteases are composed of a AAA+ partner (e.g., ClpC) and an associated peptidase (e.g., ClpP). They represent ATP-fuelled and self-compartmentalized proteolytic machines that are crucial for stress resistance and virulence. ClpC requires cooperation with adaptor proteins such as MecA for activation and complex formation with ClpP. Here, we present the cryo-EM structure of the MecA/ClpC/ClpP complex from the major pathogen Staphylococcus aureus. MecA forms a dynamic crown on top of the ClpC/ClpP complex with its substrate-binding domain positioned near the ClpC pore site, likely facilitating substrate transfer. ClpC/ClpP complex formation involves ClpC P-loops and ClpP N-terminal \u03b2-hairpins, which insert into the central ClpC threading channel and contact sites next to the ClpC ATPase center. ClpC and ClpP interactions are asymmetric and dictated by the activity states of ClpC ATPase subunits. ClpP binding increases ClpC ATPase and threading activities in a \u03b2-hairpin dependent manner, illuminating an allosteric pathway in the cooperation of ATPase and peptidase components in bacterial AAA+ proteases.", "doi": "10.1038/s42003-025-08908-w", "pmid": "41087538", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12521514"}, {"db": "pii", "key": "10.1038/s42003-025-08908-w"}], "notes": [], "created": "2025-10-25T10:21:15.566Z", "modified": "2025-10-25T10:21:15.656Z"}, {"entity": "publication", "iuid": "50dce12ee1534ab1828e5d094a809dca", "links": {"self": {"href": "https://publications.scilifelab.se/publication/50dce12ee1534ab1828e5d094a809dca.json"}, "display": {"href": "https://publications.scilifelab.se/publication/50dce12ee1534ab1828e5d094a809dca"}}, "title": "Allosteric control of the bacterial ClpC/ClpP protease and its hijacking by antibacterial peptides.", "authors": [{"family": "Jenne", "given": "Timo", "initials": "T", "orcid": "0009-0001-2033-5102", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a27284b457b4d84b7104cfc0a3d989c.json"}}, {"family": "Engelhardt", "given": "Lisa", "initials": "L", "orcid": "0009-0003-7437-2130", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb7d64c7eba74479a29e9b4cf4769b81.json"}}, {"family": "Baronaite", "given": "Ieva", "initials": "I", "orcid": "0009-0006-5515-8528", "researcher": {"href": "https://publications.scilifelab.se/researcher/afecab33e8a94b218741ab24bdb13f19.json"}}, {"family": "Levy", "given": "Dorit", "initials": "D"}, {"family": "Riven", "given": "Inbal", "initials": "I"}, {"family": "Malolepszy", "given": "Maciej", "initials": "M", "orcid": "0009-0000-9501-5990", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd88f5c57b7e4a6480d1716eca601748.json"}}, {"family": "Azinas", "given": "Stavros", "initials": "S", "orcid": "0000-0002-3744-9229", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4ec0cb5b5df4b4f89780ce3a08efc89.json"}}, {"family": "Sych", "given": "Taras", "initials": "T"}, {"family": "Sezgin", "given": "Erdinc", "initials": "E"}, {"family": "Flemming", "given": "Dirk", "initials": "D", "orcid": "0000-0002-1528-5032", "researcher": {"href": "https://publications.scilifelab.se/researcher/64abbbdb3c624cd4acaf2bebdbd27e82.json"}}, {"family": "Sinning", "given": "Irmgard", "initials": "I", "orcid": "0000-0001-9127-4477", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c8d58ff4cd24b05b4f23e4f4ef471ad.json"}}, {"family": "Haran", "given": "Gilad", "initials": "G", "orcid": "0000-0003-1837-9779", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebd2c5d7c4e649dd8ed69fc4c6ac6b8d.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Mogk", "given": "Axel", "initials": "A", "orcid": "0000-0003-3674-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/56a1d7fc519743029c9ae615086d8093.json"}}], "type": "journal article", "published": "2025-09-29", "journal": {"title": "EMBO J.", "issn": "1460-2075", "issn-l": "0261-4189"}, "abstract": "The hexameric AAA+ protein ClpC, combined with peptidase ClpP, forms a critical ATP-dependent protease in bacteria, essential for virulence. ClpC is usually repressed in an inactive resting state, where two ClpC spirals interact via coiled-coil M-domains. Antibacterial peptides and partner proteins trigger ClpC activation by binding to its N-terminal domain (NTD). This study reveals that the NTD stabilizes the resting state through multiple anchoring points to M-domains and ATPase domains. The same NTD sites also serve as binding sites for adaptor proteins and substrates carrying phosphorylated arginines (pArg), disrupting resting state interactions and promoting active ClpC hexamer formation. This coupling ensures that ClpC activation aligns with substrate and partner protein availability. Toxic peptides exploit this regulatory mechanism, leading to continuous ClpC activation and harmful, uncontrolled proteolysis. These findings highlight the dual role of the NTD in maintaining resting state stability and mediating activation, emphasizing its critical role in bacterial protease regulation and its potential as a drug target.", "doi": "10.1038/s44318-025-00575-1", "pmid": "41023306", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s44318-025-00575-1"}], "notes": [], "created": "2025-10-25T10:20:13.858Z", "modified": "2025-10-25T10:20:15.032Z"}, {"entity": "publication", "iuid": "3cc6abe50acb4e6490f16794c487bd1b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3cc6abe50acb4e6490f16794c487bd1b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3cc6abe50acb4e6490f16794c487bd1b"}}, "title": "Uromodulin velcro sheets and their interaction with uropathogenic E. coli", "authors": [{"family": "Banjara", "given": "Suresh", "initials": "S", "orcid": "0000-0002-2123-8101", "researcher": {"href": "https://publications.scilifelab.se/researcher/b935b5b29c77445aa2e9e4ccd76afd4c.json"}}, {"family": "Wang", "given": "Han", "initials": "H", "orcid": "0000-0002-6445-2095", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a6c888a8fa948a496030381158af8fb.json"}}, {"family": "Schaeffer", "given": "C\u00e9line", "initials": "C", "orcid": "0000-0001-5883-3951", "researcher": {"href": "https://publications.scilifelab.se/researcher/42307cb5448843d6ab2c6f449da28c57.json"}}, {"family": "Stsiapanava", "given": "Alena", "initials": "A", "orcid": "0000-0001-6560-011X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7dd9089728fe4d41ab4b6db272e3ed76.json"}}, {"family": "Sandin", "given": "Sara", "initials": "S", "orcid": "0000-0001-6071-2761", "researcher": {"href": "https://publications.scilifelab.se/researcher/a52c9c37f07b465781e64958a0edb780.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Okumura", "given": "Hiroki", "initials": "H", "orcid": "0000-0001-6222-9634", "researcher": {"href": "https://publications.scilifelab.se/researcher/081a2481c86944cfbb399be7b5400620.json"}}, {"family": "Rampoldi", "given": "Luca", "initials": "L", "orcid": "0000-0002-0544-7042", "researcher": {"href": "https://publications.scilifelab.se/researcher/e09ff90439784c1f81cf41b93e9fcede.json"}}, {"family": "Sandblad", "given": "Linda", "initials": "L", "orcid": "0000-0003-3492-3287", "researcher": {"href": "https://publications.scilifelab.se/researcher/070825e0190a4e9a932e79663d2bc89f.json"}}, {"family": "Jovine", "given": "Luca", "initials": "L", "orcid": "0000-0002-2679-6946", "researcher": {"href": "https://publications.scilifelab.se/researcher/8507a7657f6b434ebc572453aa172b1e.json"}}], "type": "posted-content", "published": "2025-05-11", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.05.09.653020", "pmid": null, "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [], "notes": [], "created": "2025-11-17T11:19:47.083Z", "modified": "2025-12-18T19:16:01.842Z"}, {"entity": "publication", "iuid": "db72b1430ff149429d4ed6274c089a9b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/db72b1430ff149429d4ed6274c089a9b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/db72b1430ff149429d4ed6274c089a9b"}}, "title": "Unmasking AlphaFold to integrate experiments and predictions in multimeric complexes.", "authors": [{"family": "Mirabello", "given": "Claudio", "initials": "C", "orcid": "0000-0001-7868-034X", "researcher": {"href": "https://publications.scilifelab.se/researcher/00052b54a3d24fd4a6e648f987d15e5f.json"}}, {"family": "Wallner", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0002-3772-8279", "researcher": {"href": "https://publications.scilifelab.se/researcher/108086b7b06e4247b332ff4a119b97a5.json"}}, {"family": "Nystedt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-7809-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0af5a168baa4b00a6fab8d3447ebfb4.json"}}, {"family": "Azinas", "given": "Stavros", "initials": "S", "orcid": "0000-0002-3744-9229", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4ec0cb5b5df4b4f89780ce3a08efc89.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}], "type": "journal article", "published": "2024-10-09", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "8724", "issn-l": "2041-1723"}, "abstract": "Since the release of AlphaFold, researchers have actively refined its predictions and attempted to integrate it into existing pipelines for determining protein structures. These efforts have introduced a number of functionalities and optimisations at the latest Critical Assessment of protein Structure Prediction edition (CASP15), resulting in a marked improvement in the prediction of multimeric protein structures. However, AlphaFold's capability of predicting large protein complexes is still limited and integrating experimental data in the prediction pipeline is not straightforward. In this study, we introduce AF_unmasked to overcome these limitations. Our results demonstrate that AF_unmasked can integrate experimental information to build larger or hard to predict protein assemblies with high confidence. The resulting predictions can help interpret and augment experimental data. This approach generates high quality (DockQ score > 0.8) structures even when little to no evolutionary information is available and imperfect experimental structures are used as a starting point. AF_unmasked is developed and optimised to fill incomplete experimental structures (structural inpainting), which may provide insights into protein dynamics. In summary, AF_unmasked provides an easy-to-use method that efficiently integrates experiments to predict large protein complexes more confidently.", "doi": "10.1038/s41467-024-52951-w", "pmid": "39379372", "labels": {"Bioinformatics Support, Infrastructure and Training": "Technology development", "Cryo-EM": "Service", "Bioinformatics (NBIS)": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC11461844"}, {"db": "pii", "key": "10.1038/s41467-024-52951-w"}], "notes": [], "created": "2024-11-08T10:09:12.989Z", "modified": "2024-11-15T15:09:44.609Z"}, {"entity": "publication", "iuid": "7c79186548374383ba38269c18eb530b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7c79186548374383ba38269c18eb530b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7c79186548374383ba38269c18eb530b"}}, "title": "Insights into the structure-function relationship of the NorQ/NorD chaperones from Paracoccus denitrificans reveal shared principles of interacting MoxR AAA+/VWA domain proteins.", "authors": [{"family": "Kahle", "given": "Maximilian", "initials": "M"}, {"family": "Appelgren", "given": "Sofia", "initials": "S"}, {"family": "Elofsson", "given": "Arne", "initials": "A"}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "\u00c4delroth", "given": "Pia", "initials": "P", "orcid": "0000-0003-0853-6785", "researcher": {"href": "https://publications.scilifelab.se/researcher/b798b3a524114a62b4132d17cb34f8ea.json"}}], "type": "journal article", "published": "2023-02-28", "journal": {"title": "BMC Biol.", "issn": "1741-7007", "volume": "21", "issue": "1", "pages": "47", "issn-l": "1741-7007"}, "abstract": "NorQ, a member of the MoxR-class of AAA+ ATPases, and NorD, a protein containing a Von Willebrand Factor Type A (VWA) domain, are essential for non-heme iron (FeB) cofactor insertion into cytochrome c-dependent nitric oxide reductase (cNOR). cNOR catalyzes NO reduction, a key step of bacterial denitrification. This work aimed at elucidating the specific mechanism of NorQD-catalyzed FeB insertion, and the general mechanism of the MoxR/VWA interacting protein families.\n\nWe show that NorQ-catalyzed ATP hydrolysis, an intact VWA domain in NorD, and specific surface carboxylates on cNOR are all features required for cNOR activation. Supported by BN-PAGE, low-resolution cryo-EM structures of NorQ and the NorQD complex show that NorQ forms a circular hexamer with a monomer of NorD binding both to the side and to the central pore of the NorQ ring. Guided by AlphaFold predictions, we assign the density that \"plugs\" the NorQ ring pore to the VWA domain of NorD with a protruding \"finger\" inserting through the pore and suggest this binding mode to be general for MoxR/VWA couples.\n\nBased on our results, we present a tentative model for the mechanism of NorQD-catalyzed cNOR remodeling and suggest many of its features to be applicable to the whole MoxR/VWA family.", "doi": "10.1186/s12915-023-01546-w", "pmid": "36855050", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9976466"}, {"db": "pii", "key": "10.1186/s12915-023-01546-w"}], "notes": [], "created": "2023-03-07T19:05:57.954Z", "modified": "2023-12-04T10:02:06.501Z"}, {"entity": "publication", "iuid": "6d4a622470314113a2e69dc4797c1cd2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6d4a622470314113a2e69dc4797c1cd2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6d4a622470314113a2e69dc4797c1cd2"}}, "title": "Coupling Lipid Nanoparticle Structure and Automated Single Particle Composition Analysis to Design Phospholipase Responsive Nanocarriers.", "authors": [{"family": "Barriga", "given": "Hanna M G", "initials": "HMG", "orcid": "0000-0002-2530-5332", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4bb3736c5e843018c6d245c0a584ece.json"}}, {"family": "Pence", "given": "Isaac J", "initials": "IJ", "orcid": "0000-0002-5635-1374", "researcher": {"href": "https://publications.scilifelab.se/researcher/87335a69752342798f15de8174337a3d.json"}}, {"family": "Holme", "given": "Margaret N", "initials": "MN", "orcid": "0000-0002-7314-9493", "researcher": {"href": "https://publications.scilifelab.se/researcher/33c5e475e13343eeabbc47c81c238e41.json"}}, {"family": "Doutch", "given": "James J", "initials": "JJ", "orcid": "0000-0003-0747-8368", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e1b2f6a54554068b76215bdc2554b61.json"}}, {"family": "Penders", "given": "Jelle", "initials": "J", "orcid": "0000-0002-5232-917X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b4d1a5b63934ad1876d4615f944bf5d.json"}}, {"family": "Nele", "given": "Valeria", "initials": "V", "orcid": "0000-0002-7263-7209", "researcher": {"href": "https://publications.scilifelab.se/researcher/dee5a93c05ea42ae853437cfe22d9383.json"}}, {"family": "Thomas", "given": "Michael R", "initials": "MR", "orcid": "0000-0001-7795-9648", "researcher": {"href": "https://publications.scilifelab.se/researcher/c898ca728237445a8ee4c7e6e5b053bc.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Stevens", "given": "Molly M", "initials": "MM", "orcid": "0000-0002-1146-7090", "researcher": {"href": "https://publications.scilifelab.se/researcher/11363a4ab6a749e69fbb0876b52a0060.json"}}], "type": "journal article", "published": "2022-03-31", "journal": {"title": "Adv Mater", "issn": "1521-4095", "pages": "e2200839", "issn-l": null}, "abstract": "Lipid nanoparticles (LNPs) are versatile structures with tunable physicochemical properties that are ideally suited as a platform for vaccine delivery and RNA therapeutics. A key barrier to LNP rational design is the inability to relate composition and structure to intracellular processing and function. Here we combine Single Particle Automated Raman Trapping Analysis (SPARTA\u00ae ) with small angle scattering (SAXS / SANS) techniques to link LNP composition with internal structure and morphology and to monitor dynamic LNP - phospholipase D (PLD) interactions. Our analysis demonstrates that phospholipase D, a key intracellular trafficking mediator, can access the entire LNP lipid membrane to generate stable, anionic LNPs. PLD activity on vesicles with matched amounts of enzyme substrate was an order of magnitude lower, indicating that the LNP lipid membrane structure can be used to control enzyme interactions. This represents an opportunity to design enzyme-responsive LNP solutions for stimuli-responsive delivery and diseases where PLD is dysregulated. This article is protected by copyright. All rights reserved.", "doi": "10.1002/adma.202200839", "pmid": "35358374", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [], "notes": [], "created": "2022-04-08T16:00:50.365Z", "modified": "2022-04-08T16:00:50.677Z"}, {"entity": "publication", "iuid": "d115ad4696a443b0b421db0cdfd1f465", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d115ad4696a443b0b421db0cdfd1f465.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d115ad4696a443b0b421db0cdfd1f465"}}, "title": "The structure of neurofibromin isoform 2 reveals different functional states.", "authors": [{"family": "Naschberger", "given": "Andreas", "initials": "A"}, {"family": "Baradaran", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-6096-9169", "researcher": {"href": "https://publications.scilifelab.se/researcher/2af7262546e54fc3a36f3bac03e15a79.json"}}, {"family": "Rupp", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-3300-6965", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe0f75c058924439946979522422acfc.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}], "type": "journal article", "published": "2021-10-27", "journal": {"title": "Nature", "issn": "1476-4687", "issn-l": "0028-0836", "volume": null, "issue": null, "pages": null}, "abstract": "The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to dysfunction in the protein neurofibromin (Nf1)1,2. As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. We determined the human Nf1 dimer structure at an overall resolution of 3.3 \u00c5. The cryo-electron microscopy structure reveals domain organization and structural details of the Nf1 exon 23a splicing3 isoform 2 in a closed, self-inhibited, Zn-stabilized state and an open state. In the closed conformation, HEAT/ARM core domains shield the GTPase-activating protein-related domain (GRD) so that Ras binding is sterically inhibited. In a distinctly different, open conformation of one protomer, a large-scale movement of the GRD occurs, which is necessary to access Ras, whereas Sec14-PH reorients to allow interaction with the cellular membrane4. Zn incubation of Nf1 leads to reduced Ras-GAP activity with both protomers in the self-inhibited, closed conformation stabilized by a Zn binding site between the N-HEAT/ARM domain and the GRD-Sec14-PH linker. The transition between closed, self-inhibited states of Nf1 and open states provides guidance for targeted studies deciphering the complex molecular mechanism behind the widespread neurofibromatosis syndrome and Nf1 dysfunction in carcinogenesis.", "doi": "10.1038/s41586-021-04024-x", "pmid": "34707296", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-021-04024-x"}], "notes": [], "created": "2021-11-03T13:45:56.999Z", "modified": "2021-11-10T12:21:33.839Z"}, {"entity": "publication", "iuid": "6c9beebec3bf4e008aa3f11261cfa6e6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c9beebec3bf4e008aa3f11261cfa6e6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c9beebec3bf4e008aa3f11261cfa6e6"}}, "title": "A simple pressure-assisted method for MicroED specimen preparation.", "authors": [{"family": "Zhao", "given": "Jingjing", "initials": "J", "orcid": "0000-0001-8444-6883", "researcher": {"href": "https://publications.scilifelab.se/researcher/3fbe7f2ca29941ce98c38ca6bf78c534.json"}}, {"family": "Xu", "given": "Hongyi", "initials": "H", "orcid": "0000-0002-8271-3906", "researcher": {"href": "https://publications.scilifelab.se/researcher/f112e6110df1446bbfb2679518da45d8.json"}}, {"family": "Lebrette", "given": "Hugo", "initials": "H", "orcid": "0000-0002-8081-181X", "researcher": {"href": "https://publications.scilifelab.se/researcher/17ace145c59b4e8695a5c9b95fe81b92.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Taberman", "given": "Helena", "initials": "H"}, {"family": "H\u00f6gbom", "given": "Martin", "initials": "M", "orcid": "0000-0001-5574-9383", "researcher": {"href": "https://publications.scilifelab.se/researcher/d968fcccace74b689185bb9fa2d33bf8.json"}}, {"family": "Zou", "given": "Xiaodong", "initials": "X", "orcid": "0000-0001-6748-6656", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9bd566204e3499db43d53f2adf626e0.json"}}], "type": "journal article", "published": "2021-08-19", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "5036", "issn-l": "2041-1723"}, "abstract": "Micro-crystal electron diffraction (MicroED) has shown great potential for structure determination of macromolecular crystals too small for X-ray diffraction. However, specimen preparation remains a major bottleneck. Here, we report a simple method for preparing MicroED specimens, named Preassis, in which excess liquid is removed through an EM grid with the assistance of pressure. We show the ice thicknesses can be controlled by tuning the pressure in combination with EM grids with appropriate carbon hole sizes. Importantly, Preassis can handle a wide range of protein crystals grown in various buffer conditions including those with high viscosity, as well as samples with low crystal concentrations. Preassis is a simple and universal method for MicroED specimen preparation, and will significantly broaden the applications of MicroED.", "doi": "10.1038/s41467-021-25335-7", "pmid": "34413316", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-021-25335-7"}, {"db": "pmc", "key": "PMC8377027"}], "notes": [], "created": "2021-12-14T12:47:04.167Z", "modified": "2023-12-04T10:18:11.258Z"}, {"entity": "publication", "iuid": "a9d191eeacbf4b7b94a4e1366b774166", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a9d191eeacbf4b7b94a4e1366b774166.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a9d191eeacbf4b7b94a4e1366b774166"}}, "title": "Using RELION software within the Scipion framework.", "authors": [{"family": "Sharov", "given": "Grigory", "initials": "G", "orcid": "0000-0002-6930-4999", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3cd747674414ac1a94650c94d77cac6.json"}}, {"family": "Morado", "given": "Dustin R", "initials": "DR", "orcid": "0000-0003-4693-3220", "researcher": {"href": "https://publications.scilifelab.se/researcher/eef09b7a95b64a699900bae6a5390e31.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "de la Rosa-Trev\u00edn", "given": "Jos\u00e9 Miguel", "initials": "JM", "orcid": "0000-0002-3320-1269", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9c797d9907249f0bb608c1340ac6f5c.json"}}], "type": "journal article", "published": "2021-04-01", "journal": {"title": "Acta Crystallogr D Struct Biol", "issn": "2059-7983", "issn-l": "2059-7983", "volume": "77", "issue": "4", "pages": "403-410"}, "abstract": "Scipion is a modular image-processing framework that integrates several software packages under a unified interface while taking care of file formats and conversions. Here, new developments and capabilities of the Scipion plugin for the widely used RELION software package are presented and illustrated with an image-processing pipeline for published data. The user interfaces of Scipion and RELION are compared and the key differences are highlighted, allowing this manuscript to be used as a guide for both new and experienced users of this software. Different on-the-fly image-processing options are also discussed, demonstrating the flexibility of the Scipion framework.", "doi": "10.1107/S2059798321001856", "pmid": "33825701", "labels": {"Cryo-EM": "Technology development"}, "xrefs": [{"db": "pii", "key": "S2059798321001856"}, {"db": "pmc", "key": "PMC8025880"}], "notes": [], "created": "2021-05-19T22:52:58.831Z", "modified": "2023-12-04T10:06:15.737Z"}, {"entity": "publication", "iuid": "f44fcf7d5d8c4115b4eba8d5c8fbd3f1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f44fcf7d5d8c4115b4eba8d5c8fbd3f1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f44fcf7d5d8c4115b4eba8d5c8fbd3f1"}}, "title": "Cryo-EM structure of native human uromodulin, a zona pellucida module polymer.", "authors": [{"family": "Stsiapanava", "given": "Alena", "initials": "A", "orcid": "0000-0001-6560-011X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7dd9089728fe4d41ab4b6db272e3ed76.json"}}, {"family": "Xu", "given": "Chenrui", "initials": "C", "orcid": "0000-0002-5605-728X", "researcher": {"href": "https://publications.scilifelab.se/researcher/619340ff51bb4d2f8025398a3e3c8135.json"}}, {"family": "Brunati", "given": "Martina", "initials": "M", "orcid": "0000-0002-1010-0836", "researcher": {"href": "https://publications.scilifelab.se/researcher/da793018cb7b4d89915361d08944fe10.json"}}, {"family": "Zamora-Caballero", "given": "Sara", "initials": "S", "orcid": "0000-0003-4717-8845", "researcher": {"href": "https://publications.scilifelab.se/researcher/c561b8843e9f41de9c409f7a681c8663.json"}}, {"family": "Schaeffer", "given": "C\u00e9line", "initials": "C", "orcid": "0000-0001-5883-3951", "researcher": {"href": "https://publications.scilifelab.se/researcher/42307cb5448843d6ab2c6f449da28c57.json"}}, {"family": "Bokhove", "given": "Marcel", "initials": "M", "orcid": "0000-0001-7241-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/f695b97f38d24caabea3d3c3d59f0890.json"}}, {"family": "Han", "given": "Ling", "initials": "L", "orcid": "0000-0001-9310-4789", "researcher": {"href": "https://publications.scilifelab.se/researcher/1f38b9eaca93474280189bb93b118817.json"}}, {"family": "Hebert", "given": "Hans", "initials": "H", "orcid": "0000-0002-3220-9402", "researcher": {"href": "https://publications.scilifelab.se/researcher/6868ee027bb14470b2d10c762d9b751b.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Yasumasu", "given": "Shigeki", "initials": "S", "orcid": "0000-0003-4295-477X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1a2c2d36d89419da0e3242bf2c85327.json"}}, {"family": "Rampoldi", "given": "Luca", "initials": "L", "orcid": "0000-0002-0544-7042", "researcher": {"href": "https://publications.scilifelab.se/researcher/e09ff90439784c1f81cf41b93e9fcede.json"}}, {"family": "Wu", "given": "Bin", "initials": "B", "orcid": "0000-0002-0883-8006", "researcher": {"href": "https://publications.scilifelab.se/researcher/76dd84c8134245d48bf28f63511fa1ba.json"}}, {"family": "Jovine", "given": "Luca", "initials": "L", "orcid": "0000-0002-2679-6946", "researcher": {"href": "https://publications.scilifelab.se/researcher/8507a7657f6b434ebc572453aa172b1e.json"}}], "type": "journal article", "published": "2020-12-15", "journal": {"title": "EMBO J.", "issn": "1460-2075", "volume": "39", "issue": "24", "pages": "e106807", "issn-l": "0261-4189"}, "abstract": "Assembly of extracellular filaments and matrices mediating fundamental biological processes such as morphogenesis, hearing, fertilization, and antibacterial defense is driven by a ubiquitous polymerization module known as zona pellucida (ZP) \"domain\". Despite the conservation of this element from hydra to humans, no detailed information is available on the filamentous conformation of any ZP module protein. Here, we report a cryo-electron microscopy study of uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant protein in human urine and an archetypal ZP module-containing molecule, in its mature homopolymeric state. UMOD forms a one-start helix with an unprecedented 180-degree twist between subunits enfolded by interdomain linkers that have completely reorganized as a result of propeptide dissociation. Lateral interaction between filaments in the urine generates sheets exposing a checkerboard of binding sites to capture uropathogenic bacteria, and UMOD-based models of heteromeric vertebrate egg coat filaments identify a common sperm-binding region at the interface between subunits.", "doi": "10.15252/embj.2020106807", "pmid": "33196145", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7737619"}, {"db": "PDB", "key": "6TQK"}, {"db": "PDB", "key": "6TQL"}], "notes": [], "created": "2020-11-17T10:27:09.459Z", "modified": "2021-11-10T12:45:16.114Z"}, {"entity": "publication", "iuid": "f4b79cf485ae4ae2b999a8ce542884b9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f4b79cf485ae4ae2b999a8ce542884b9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f4b79cf485ae4ae2b999a8ce542884b9"}}, "title": "Structural basis for the increased processivity of D-family DNA polymerases in complex with PCNA.", "authors": [{"family": "Madru", "given": "Cl\u00e9ment", "initials": "C"}, {"family": "Henneke", "given": "Ghislaine", "initials": "G"}, {"family": "Raia", "given": "Pierre", "initials": "P", "orcid": "0000-0003-3469-1922", "researcher": {"href": "https://publications.scilifelab.se/researcher/bdf3d3b11b384d52ba1bc00e7173b44b.json"}}, {"family": "Hugonneau-Beaufet", "given": "In\u00e8s", "initials": "I"}, {"family": "Pehau-Arnaudet", "given": "G\u00e9rard", "initials": "G"}, {"family": "England", "given": "Patrick", "initials": "P"}, {"family": "Lindahl", "given": "Erik", "initials": "E"}, {"family": "Delarue", "given": "Marc", "initials": "M"}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Sauguet", "given": "Ludovic", "initials": "L"}], "type": "journal article", "published": "2020-03-27", "journal": {"volume": "11", "issn": "2041-1723", "issue": "1", "pages": "1591", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Replicative DNA polymerases (DNAPs) have evolved the ability to copy the genome with high processivity and fidelity. In Eukarya and Archaea, the processivity of replicative DNAPs is greatly enhanced by its binding to the proliferative cell nuclear antigen (PCNA) that encircles the DNA. We determined the cryo-EM structure of the DNA-bound PolD-PCNA complex from Pyrococcus abyssi at 3.77 \u00c5. Using an integrative structural biology approach - combining cryo-EM, X-ray crystallography, protein-protein interaction measurements, and activity assays - we describe the molecular basis for the interaction and cooperativity between a replicative DNAP and PCNA. PolD recruits PCNA via a complex mechanism, which requires two different PIP-boxes. We infer that the second PIP-box, which is shared with the eukaryotic Pol\u03b1 replicative DNAP, plays a dual role in binding either PCNA or primase, and could be a master switch between an initiation and a processive phase during replication.", "doi": "10.1038/s41467-020-15392-9", "pmid": "32221299", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15392-9"}, {"db": "pmc", "key": "PMC7101311"}], "notes": [], "created": "2020-04-16T10:31:32.697Z", "modified": "2021-11-10T12:52:47.618Z"}, {"entity": "publication", "iuid": "71ffe4b89f0949ca9a47381a766b9468", "links": {"self": {"href": "https://publications.scilifelab.se/publication/71ffe4b89f0949ca9a47381a766b9468.json"}, "display": {"href": "https://publications.scilifelab.se/publication/71ffe4b89f0949ca9a47381a766b9468"}}, "title": "Electron cryo-microscopy of bacteriophage PR772 reveals the elusive vertex complex and the capsid architecture.", "authors": [{"family": "Reddy", "given": "Hemanth Kn", "initials": "HK", "orcid": "0000-0002-4698-8005", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e5c3a002d56469d807a71f8540f1fbe.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Hajdu", "given": "Janos", "initials": "J", "orcid": "0000-0002-3747-2760", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1aa4ac672a6499dbb44cdd867d73fea.json"}}, {"family": "Svenda", "given": "Martin", "initials": "M", "orcid": "0000-0003-1162-8285", "researcher": {"href": "https://publications.scilifelab.se/researcher/72864e5d60f746368c9dfce4b22b4e26.json"}}], "type": "journal article", "published": "2019-09-12", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "8", "issue": null, "pages": null, "issn-l": "2050-084X"}, "abstract": "Bacteriophage PR772, a member of the Tectiviridae family, has a 70 nm diameter icosahedral protein capsid that encapsulates a lipid membrane, dsDNA, and various internal proteins. An icosahedrally averaged CryoEM reconstruction of the wild-type virion and a localized reconstruction of the vertex region reveal the composition and the structure of the vertex complex along with new protein conformations that play a vital role in maintaining the capsid architecture of the virion. The overall resolution of the virion is 2.75 \u00c5, while the resolution of the protein capsid is 2.3 \u00c5. The conventional penta-symmetron formed by the capsomeres is replaced by a large vertex complex in the pseudo T = 25 capsid. All the vertices contain the host-recognition protein, P5; two of these vertices show the presence of the receptor-binding protein, P2. The 3D structure of the vertex complex shows interactions with the viral membrane, indicating a possible mechanism for viral infection.", "doi": "10.7554/eLife.48496", "pmid": "31513011", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "48496"}, {"db": "pmc", "key": "PMC6750898"}, {"db": "PDB", "key": "6Q5U"}], "notes": [], "created": "2019-11-15T17:56:08.210Z", "modified": "2021-06-18T14:08:15.365Z"}, {"entity": "publication", "iuid": "28b811ab5a9b428a84a34ac51f15102f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/28b811ab5a9b428a84a34ac51f15102f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/28b811ab5a9b428a84a34ac51f15102f"}}, "title": "Toxic Activation of an AAA+ Protease by the Antibacterial Drug Cyclomarin A.", "authors": [{"family": "Maurer", "given": "Michael", "initials": "M"}, {"family": "Linder", "given": "Daniela", "initials": "D"}, {"family": "Franke", "given": "Kamila B", "initials": "KB"}, {"family": "J\u00e4ger", "given": "Jasmin", "initials": "J"}, {"family": "Taylor", "given": "Gabrielle", "initials": "G"}, {"family": "Gloge", "given": "Felix", "initials": "F"}, {"family": "Gremer", "given": "Sebastian", "initials": "S"}, {"family": "Le Breton", "given": "Laura", "initials": "L"}, {"family": "Mayer", "given": "Matthias P", "initials": "MP"}, {"family": "Weber-Ban", "given": "Eilika", "initials": "E"}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Bukau", "given": "Bernd", "initials": "B"}, {"family": "Mogk", "given": "Axel", "initials": "A"}], "type": "journal article", "published": "2019-08-15", "journal": {"title": "Cell Chem Biol", "issn": "2451-9448", "volume": "26", "issue": "8", "pages": "1169-1179.e4", "issn-l": null}, "abstract": "ATP-driven bacterial AAA+ proteases have been recognized as drug targets. They possess an AAA+ protein (e.g., ClpC), which threads substrate proteins into an associated peptidase (e.g., ClpP). ATPase activity and substrate selection of AAA+ proteins are regulated by adapter proteins that bind to regulatory domains, such as the N-terminal domain (NTD). The antibacterial peptide Cyclomarin A (CymA) kills Mycobacterium tuberculosis cells by binding to the NTD of ClpC. How CymA affects ClpC function is unknown. Here, we reveal the mechanism of CymA-induced toxicity. We engineered a CymA-sensitized ClpC chimera and show that CymA activates ATPase and proteolytic activities. CymA mimics adapter binding and enables autonomous protein degradation by ClpC/ClpP with relaxed substrate selectivity. We reconstitute CymA toxicity in E. coli cells expressing engineered ClpC and ClpP, demonstrating that gain of uncontrolled proteolytic activity causes cell death. This validates drug-induced overriding of AAA+ protease activity control as effective antibacterial strategy.", "doi": "10.1016/j.chembiol.2019.05.008", "pmid": "31204287", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "S2451-9456(19)30177-1"}], "notes": [], "created": "2019-06-24T13:42:02.192Z", "modified": "2021-07-05T17:22:27.636Z"}, {"entity": "publication", "iuid": "cd2c79c36dce474887bcfa22c3b80b5d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cd2c79c36dce474887bcfa22c3b80b5d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cd2c79c36dce474887bcfa22c3b80b5d"}}, "title": "Structure of the DP1\u2013DP2 PolD complex bound with DNA and its implications for the evolutionary history of DNA and RNA polymerases", "authors": [{"family": "Raia", "given": "Pierre", "initials": "P", "orcid": "0000-0003-3469-1922", "researcher": {"href": "https://publications.scilifelab.se/researcher/bdf3d3b11b384d52ba1bc00e7173b44b.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Henry", "given": "Etienne", "initials": "E"}, {"family": "Pehau-Arnaudet", "given": "G\u00e9rard", "initials": "G"}, {"family": "Br\u00fbl\u00e9", "given": "S\u00e9bastien", "initials": "S", "orcid": "0000-0002-8797-6748", "researcher": {"href": "https://publications.scilifelab.se/researcher/d4434962f7e74f27912471002ac84cf4.json"}}, {"family": "B\u00e9guin", "given": "Pierre", "initials": "P"}, {"family": "Henneke", "given": "Ghislaine", "initials": "G"}, {"family": "Lindahl", "given": "Erik", "initials": "E"}, {"family": "Delarue", "given": "Marc", "initials": "M"}, {"family": "Sauguet", "given": "Ludovic", "initials": "L", "orcid": "0000-0002-1259-6601", "researcher": {"href": "https://publications.scilifelab.se/researcher/157797855bd0495db5f788432d1e330f.json"}}], "type": "journal-article", "published": "2019-01-18", "journal": {"title": "PLoS Biol.", "issn": "1545-7885", "volume": "17", "issue": "1", "pages": "e3000122", "issn-l": "1544-9173"}, "abstract": "PolD is an archaeal replicative DNA polymerase (DNAP) made of a proofreading exonuclease subunit (DP1) and a larger polymerase catalytic subunit (DP2). Recently, we reported the individual crystal structures of the DP1 and DP2 catalytic cores, thereby revealing that PolD is an atypical DNAP that has all functional properties of a replicative DNAP but with the catalytic core of an RNA polymerase (RNAP). We now report the DNA-bound cryo-electron microscopy (cryo-EM) structure of the heterodimeric DP1-DP2 PolD complex from Pyrococcus abyssi, revealing a unique DNA-binding site. Comparison of PolD and RNAPs extends their structural similarities and brings to light the minimal catalytic core shared by all cellular transcriptases. Finally, elucidating the structure of the PolD DP1-DP2 interface, which is conserved in all eukaryotic replicative DNAPs, clarifies their evolutionary relationships with PolD and sheds light on the domain acquisition and exchange mechanism that occurred during the evolution of the eukaryotic replisome.", "doi": "10.1371/journal.pbio.3000122", "pmid": "30657780", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pii", "key": "PBIOLOGY-D-18-00775"}, {"db": "pmc", "key": "PMC6355029"}], "notes": [], "created": "2019-02-12T09:40:03.456Z", "modified": "2021-06-21T13:42:01.143Z"}, {"entity": "publication", "iuid": "92dba4d4ec6f45f9ad59022513e674eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/92dba4d4ec6f45f9ad59022513e674eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/92dba4d4ec6f45f9ad59022513e674eb"}}, "title": "Cryo-EM structure of the yeast respiratory supercomplex.", "authors": [{"family": "Rathore", "given": "Sorbhi", "initials": "S", "orcid": "0000-0001-9178-1006", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c2293f9f60f44cfa47f1e3691c1309d.json"}}, {"family": "Berndtsson", "given": "Jens", "initials": "J", "orcid": "0000-0001-6627-8134", "researcher": {"href": "https://publications.scilifelab.se/researcher/7620a5c7c0f245a28771d57d7179abbd.json"}}, {"family": "Marin-Buera", "given": "Lorena", "initials": "L"}, {"family": "Conrad", "given": "Julian", "initials": "J"}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Brzezinski", "given": "Peter", "initials": "P", "orcid": "0000-0003-3860-4988", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3314030ecf94791a713a068d4926c20.json"}}, {"family": "Ott", "given": "Martin", "initials": "M", "orcid": "0000-0001-6367-3091", "researcher": {"href": "https://publications.scilifelab.se/researcher/b27b582dbd2a47bcbb0fb3194277902a.json"}}], "type": "journal article", "published": "2019-01-00", "journal": {"title": "Nat. Struct. Mol. Biol.", "issn": "1545-9985", "volume": "26", "issue": "1", "pages": "50-57", "issn-l": "1545-9985"}, "abstract": "Respiratory chain complexes execute energy conversion by connecting electron transport with proton translocation over the inner mitochondrial membrane to fuel ATP synthesis. Notably, these complexes form multi-enzyme assemblies known as respiratory supercomplexes. Here we used single-particle cryo-EM to determine the structures of the yeast mitochondrial respiratory supercomplexes III 2IV and III2IV2, at 3.2-\u00c5 and 3.5-\u00c5 resolutions, respectively. We revealed the overall architecture of the supercomplex, which deviates from the previously determined assemblies in mammals; obtained a near-atomic structure of the yeast complex IV; and identified the protein-protein and protein-lipid interactions implicated in supercomplex formation. Take together, our results demonstrate convergent evolution of supercomplexes in mitochondria that, while building similar assemblies, results in substantially different arrangements and structural solutions to support energy conversion.", "doi": "10.1038/s41594-018-0169-7", "pmid": "30598556", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41594-018-0169-7"}], "notes": [], "created": "2019-01-03T16:38:40.124Z", "modified": "2021-06-21T13:49:53.118Z"}, {"entity": "publication", "iuid": "c513594b717d41568e7a836fb7437a2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c513594b717d41568e7a836fb7437a2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c513594b717d41568e7a836fb7437a2f"}}, "title": "Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin", "authors": [{"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Vallhov", "given": "Helen", "initials": "H"}, {"family": "Holm", "given": "Tina", "initials": "T"}, {"family": "Gehrmann", "given": "Ulf", "initials": "U"}, {"family": "Andersson", "given": "Anna", "initials": "A"}, {"family": "Johansson", "given": "Catharina", "initials": "C"}, {"family": "Blom", "given": "Hans", "initials": "H", "orcid": "0000-0002-5584-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ce356a74dc84e0ea6af85397f11d869.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Scheynius", "given": "Annika", "initials": "A"}], "type": "journal-article", "published": "2018-12-00", "journal": {"volume": "8", "issn": "2045-2322", "issue": "1", "pages": null, "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is also associated with common skin disorders including atopic eczema (AE). M. sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Here we explored how MalaEx are involved in host-microbe interactions by comparing protein content of MalaEx with that of the parental yeast cells, and by investigating interactions of MalaEx with cells in the skin. Cryo-electron tomography revealed a heterogeneous population of MalaEx. iTRAQ based quantitative proteomics identified in total 2439 proteins in all replicates of which 110 were enriched in MalaEx compared to the yeast cells. Among the MalaEx enriched proteins were two of the M. sympodialis allergens, Mala s 1 and s 7. Functional experiments indicated an active binding and internalization of MalaEx into human keratinocytes and monocytes, and MalaEx were found in close proximity of the nuclei using super-resolution fluorescence 3D-SIM imaging. Our results provides new insights into host-microbe interactions, supporting that MalaEx may have a role in the sensitization and maintenance of inflammation in AE by containing enriched amounts of allergens and with their ability to interact with skin cells.", "doi": "10.1038/s41598-018-27451-9", "pmid": "29907748", "labels": {"Cryo-EM": "Service", "Global Proteomics and Proteogenomics": "Collaborative", "Integrated Microscopy Technologies Stockholm": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "jPOSTrepo", "description": "https://repository.jpostdb.org/entry/JPST000288", "key": "JPST000288"}], "notes": [], "created": "2018-06-20T09:34:38.559Z", "modified": "2024-01-16T13:48:45.085Z"}, {"entity": "publication", "iuid": "399a1658a8ac49b3b64aac51b37dfa90", "links": {"self": {"href": "https://publications.scilifelab.se/publication/399a1658a8ac49b3b64aac51b37dfa90.json"}, "display": {"href": "https://publications.scilifelab.se/publication/399a1658a8ac49b3b64aac51b37dfa90"}}, "title": "The shape of the bacterial ribosome exit tunnel affects cotranslational protein folding.", "authors": [{"family": "Kudva", "given": "Renuka", "initials": "R", "orcid": "0000-0003-0426-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/064d5e466c804d5999e2e41033766d6e.json"}}, {"family": "Tian", "given": "Pengfei", "initials": "P"}, {"family": "Pardo-Avila", "given": "F\u00e1tima", "initials": "F"}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Best", "given": "Robert B", "initials": "RB", "orcid": "0000-0002-7893-3543", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a43cec408bf4353b6d89044c726948d.json"}}, {"family": "Bernstein", "given": "Harris D", "initials": "HD", "orcid": "0000-0002-4941-3741", "researcher": {"href": "https://publications.scilifelab.se/researcher/052958cf88b64effb56ec00a9af79471.json"}}, {"family": "von Heijne", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-4490-8569", "researcher": {"href": "https://publications.scilifelab.se/researcher/f663c0a9e9e1455cbbf8e6aea13af4a9.json"}}], "type": "journal article", "published": "2018-11-26", "journal": {"volume": "7", "issn": "2050-084X", "issue": null, "pages": null, "title": "Elife", "issn-l": "2050-084X"}, "abstract": "The E. coli ribosome exit tunnel can accommodate small folded proteins, while larger ones fold outside. It remains unclear, however, to what extent the geometry of the tunnel influences protein folding. Here, using E. coli ribosomes with deletions in loops in proteins uL23 and uL24 that protrude into the tunnel, we investigate how tunnel geometry determines where proteins of different sizes fold. We find that a 29-residue zinc-finger domain normally folding close to the uL23 loop folds deeper in the tunnel in uL23 \u0394loop ribosomes, while two ~ 100 residue proteins normally folding close to the uL24 loop near the tunnel exit port fold at deeper locations in uL24 \u0394loop ribosomes, in good agreement with results obtained by coarse-grained molecular dynamics simulations. This supports the idea that cotranslational folding commences once a protein domain reaches a location in the exit tunnel where there is sufficient space to house the folded structure.", "doi": "10.7554/eLife.36326", "pmid": "30475203", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "36326"}, {"db": "pmc", "key": "PMC6298777"}], "notes": [], "created": "2018-12-05T16:10:50.496Z", "modified": "2021-06-16T15:22:50.918Z"}, {"entity": "publication", "iuid": "92cab8743c914793addeffdf3501813d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/92cab8743c914793addeffdf3501813d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/92cab8743c914793addeffdf3501813d"}}, "title": "Using Scipion for stream image processing at Cryo-EM facilities", "authors": [{"family": "G\u00f3mez-Blanco", "given": "J", "initials": "J"}, {"family": "de la Rosa-Trev\u00edn", "given": "J M", "initials": "JM", "orcid": "0000-0002-3320-1269", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9c797d9907249f0bb608c1340ac6f5c.json"}}, {"family": "Marabini", "given": "R", "initials": "R"}, {"family": "del Cano", "given": "L", "initials": "L"}, {"family": "Jim\u00e9nez", "given": "A", "initials": "A"}, {"family": "Mart\u00ednez", "given": "M", "initials": "M"}, {"family": "Melero", "given": "R", "initials": "R"}, {"family": "Majtner", "given": "T", "initials": "T"}, {"family": "Maluenda", "given": "D", "initials": "D"}, {"family": "Mota", "given": "J", "initials": "J"}, {"family": "Rancel", "given": "Y", "initials": "Y"}, {"family": "Ram\u00edrez-Aportela", "given": "E", "initials": "E"}, {"family": "Vilas", "given": "J L", "initials": "JL"}, {"family": "Carroni", "given": "M", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Fleischmann", "given": "S", "initials": "S"}, {"family": "Lindahl", "given": "E", "initials": "E", "orcid": "0000-0003-1333-5398", "researcher": {"href": "https://publications.scilifelab.se/researcher/51600cedcf044bdda0f677deaeaf9fad.json"}}, {"family": "Ashton", "given": "A W", "initials": "AW"}, {"family": "Basham", "given": "M", "initials": "M"}, {"family": "Clare", "given": "D K", "initials": "DK"}, {"family": "Savage", "given": "K", "initials": "K"}, {"family": "Siebert", "given": "C A", "initials": "CA"}, {"family": "Sharov", "given": "G G", "initials": "GG"}, {"family": "Sorzano", "given": "C O S", "initials": "COS"}, {"family": "Conesa", "given": "P", "initials": "P"}, {"family": "Carazo", "given": "J M", "initials": "JM"}], "type": "journal-article", "published": "2018-10-00", "journal": {"volume": null, "issn": "1047-8477", "issue": null, "pages": null, "title": "Journal of Structural Biology", "issn-l": "1047-8477"}, "abstract": null, "doi": "10.1016/j.jsb.2018.10.001", "pmid": "30296492", "labels": {"Cryo-EM": "Technology development"}, "xrefs": [], "notes": [], "created": "2018-10-19T20:43:58.020Z", "modified": "2023-12-04T10:06:41.293Z"}, {"entity": "publication", "iuid": "123bf2cc4a644ec4bb602d2feaa85eae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/123bf2cc4a644ec4bb602d2feaa85eae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/123bf2cc4a644ec4bb602d2feaa85eae"}}, "title": "Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.", "authors": [{"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Franke", "given": "Kamila B", "initials": "KB"}, {"family": "Maurer", "given": "Michael", "initials": "M"}, {"family": "J\u00e4ger", "given": "Jasmin", "initials": "J"}, {"family": "Hantke", "given": "Ingo", "initials": "I"}, {"family": "Gloge", "given": "Felix", "initials": "F"}, {"family": "Linder", "given": "Daniela", "initials": "D"}, {"family": "Gremer", "given": "Sebastian", "initials": "S", "orcid": "0000-0003-3421-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe66266bc6c94ec59e03a94d6e3fc997.json"}}, {"family": "Turgay", "given": "K\u00fcr\u015fad", "initials": "K", "orcid": "0000-0002-8959-492X", "researcher": {"href": "https://publications.scilifelab.se/researcher/55cd714404fb4112bd7b3ed1c4328a17.json"}}, {"family": "Bukau", "given": "Bernd", "initials": "B"}, {"family": "Mogk", "given": "Axel", "initials": "A", "orcid": "0000-0003-3674-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/56a1d7fc519743029c9ae615086d8093.json"}}], "type": "journal article", "published": "2017-11-22", "journal": {"volume": "6", "issn": "2050-084X", "issue": null, "pages": null, "title": "Elife", "issn-l": "2050-084X"}, "abstract": "Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.", "doi": "10.7554/eLife.30120", "pmid": "29165246", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC5699869"}], "notes": [], "created": "2017-11-24T14:39:40.774Z", "modified": "2021-07-05T17:22:27.628Z"}, {"entity": "publication", "iuid": "daf09ae6d7c44e24bf34efb14d8edacb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/daf09ae6d7c44e24bf34efb14d8edacb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/daf09ae6d7c44e24bf34efb14d8edacb"}}, "title": "Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase.", "authors": [{"family": "Deville", "given": "C\u00e9lia", "initials": "C", "orcid": "0000-0002-0235-6735", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c716cbe85a047c595efdb2a55a7dcb6.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Franke", "given": "Kamila B", "initials": "KB"}, {"family": "Topf", "given": "Maya", "initials": "M", "orcid": "0000-0002-8185-1215", "researcher": {"href": "https://publications.scilifelab.se/researcher/de031511a9374c3f97b14433944dee8c.json"}}, {"family": "Bukau", "given": "Bernd", "initials": "B"}, {"family": "Mogk", "given": "Axel", "initials": "A", "orcid": "0000-0003-3674-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/56a1d7fc519743029c9ae615086d8093.json"}}, {"family": "Saibil", "given": "Helen R", "initials": "HR", "orcid": "0000-0002-2266-8891", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1d53e27939a416893b968a87fedd92e.json"}}], "type": "journal article", "published": "2017-08-00", "journal": {"volume": "3", "issn": "2375-2548", "issue": "8", "pages": "e1701726", "title": "Sci Adv", "issn-l": "2375-2548"}, "abstract": "Refolding aggregated proteins is essential in combating cellular proteotoxic stress. Together with Hsp70, Hsp100 chaperones, including Escherichia coli ClpB, form a powerful disaggregation machine that threads aggregated polypeptides through the central pore of tandem adenosine triphosphatase (ATPase) rings. To visualize protein disaggregation, we determined cryo-electron microscopy structures of inactive and substrate-bound ClpB in the presence of adenosine 5'-O-(3-thiotriphosphate), revealing closed AAA+ rings with a pronounced seam. In the substrate-free state, a marked gradient of resolution, likely corresponding to mobility, spans across the AAA+ rings with a dynamic hotspot at the seam. On the seam side, the coiled-coil regulatory domains are locked in a horizontal, inactive orientation. On the opposite side, the regulatory domains are accessible for Hsp70 binding, substrate targeting, and activation. In the presence of the model substrate casein, the polypeptide threads through the entire pore channel and increased nucleotide occupancy correlates with higher ATPase activity. Substrate-induced domain displacements indicate a pathway of regulated substrate transfer from Hsp70 to the ClpB pore, inside which a spiral of loops contacts the substrate. The seam pore loops undergo marked displacements, along with ordering of the regulatory domains. These asymmetric movements suggest a mechanism for ATPase activation and substrate threading during disaggregation.", "doi": "10.1126/sciadv.1701726", "pmid": "28798962", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "1701726"}, {"db": "pmc", "key": "PMC5544394"}], "notes": [], "created": "2017-10-16T16:20:48.109Z", "modified": "2021-07-05T17:22:20.822Z"}]}