{"entity": "researcher", "timestamp": "2026-07-20T12:51:16.422Z", "family": "Hauryliuk", "given": "Vasili", "initials": "V", "orcid": "0000-0003-2389-5057", "affiliations": [], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/17ea83b1d20f43f9872edbf89b275e5d.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/17ea83b1d20f43f9872edbf89b275e5d"}}, "publications": [{"entity": "publication", "iuid": "66c881219ece474bac516a8dca467e87", "links": {"self": {"href": "https://publications.scilifelab.se/publication/66c881219ece474bac516a8dca467e87.json"}, "display": {"href": "https://publications.scilifelab.se/publication/66c881219ece474bac516a8dca467e87"}}, "title": "Genome-encoded ABCF factors implicated in intrinsic antibiotic resistance in Gram-positive bacteria: VmlR2, Ard1 and CplR.", "authors": [{"family": "Obana", "given": "Nozomu", "initials": "N"}, {"family": "Takada", "given": "Hiraku", "initials": "H"}, {"family": "Crowe-McAuliffe", "given": "Caillan", "initials": "C"}, {"family": "Iwamoto", "given": "Mizuki", "initials": "M"}, {"family": "Egorov", "given": "Artyom A", "initials": "AA"}, {"family": "Wu", "given": "Kelvin J Y", "initials": "KJY"}, {"family": "Chiba", "given": "Shinobu", "initials": "S", "orcid": "0000-0003-3485-3477", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad706e1ea3274befa875504e25781986.json"}}, {"family": "Murina", "given": "Victoriia", "initials": "V"}, {"family": "Paternoga", "given": "Helge", "initials": "H"}, {"family": "Tresco", "given": "Ben I C", "initials": "BIC"}, {"family": "Nomura", "given": "Nobuhiko", "initials": "N"}, {"family": "Myers", "given": "Andrew G", "initials": "AG"}, {"family": "Atkinson", "given": "Gemma C", "initials": "GC"}, {"family": "Wilson", "given": "Daniel N", "initials": "DN", "orcid": "0000-0003-3816-3828", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd50ba35f7c74d7e9d4f42fbc49739f2.json"}}, {"family": "Hauryliuk", "given": "Vasili", "initials": "V", "orcid": "0000-0003-2389-5057", "researcher": {"href": "https://publications.scilifelab.se/researcher/17ea83b1d20f43f9872edbf89b275e5d.json"}}], "type": "journal article", "published": "2023-05-22", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "51", "issue": "9", "pages": "4536-4554", "issn-l": "0305-1048"}, "abstract": "Genome-encoded antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F subfamily (ARE-ABCFs) mediate intrinsic resistance in diverse Gram-positive bacteria. The diversity of chromosomally-encoded ARE-ABCFs is far from being fully experimentally explored. Here we characterise phylogenetically diverse genome-encoded ABCFs from Actinomycetia (Ard1 from Streptomyces capreolus, producer of the nucleoside antibiotic A201A), Bacilli (VmlR2 from soil bacterium Neobacillus vireti) and Clostridia (CplR from Clostridium perfringens, Clostridium sporogenes and Clostridioides difficile). We demonstrate that Ard1 is a narrow spectrum ARE-ABCF that specifically mediates self-resistance against nucleoside antibiotics. The single-particle cryo-EM structure of a VmlR2-ribosome complex allows us to rationalise the resistance spectrum of this ARE-ABCF that is equipped with an unusually long antibiotic resistance determinant (ARD) subdomain. We show that CplR contributes to intrinsic pleuromutilin, lincosamide and streptogramin A resistance in Clostridioides, and demonstrate that C. difficile CplR (CDIF630_02847) synergises with the transposon-encoded 23S ribosomal RNA methyltransferase Erm to grant high levels of antibiotic resistance to the C. difficile 630 clinical isolate. Finally, assisted by uORF4u, our novel tool for detection of upstream open reading frames, we dissect the translational attenuation mechanism that controls the induction of cplR expression upon an antibiotic challenge.", "doi": "10.1093/nar/gkad193", "pmid": "36951104", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10201436"}, {"db": "pii", "key": "7084601"}], "notes": [], "created": "2023-11-27T11:41:51.119Z", "modified": "2023-11-27T11:41:51.165Z"}, {"entity": "publication", "iuid": "0ae342fa95624219a707ae26e188890c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0ae342fa95624219a707ae26e188890c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0ae342fa95624219a707ae26e188890c"}}, "title": "Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics.", "authors": [{"family": "Crowe-McAuliffe", "given": "Caillan", "initials": "C"}, {"family": "Murina", "given": "Victoriia", "initials": "V"}, {"family": "Turnbull", "given": "Kathryn Jane", "initials": "KJ"}, {"family": "Huch", "given": "Susanne", "initials": "S"}, {"family": "Kasari", "given": "Marje", "initials": "M", "orcid": "0000-0002-2177-3753", "researcher": {"href": "https://publications.scilifelab.se/researcher/878f3508ac344958a0fea57329d67274.json"}}, {"family": "Takada", "given": "Hiraku", "initials": "H"}, {"family": "Nersisyan", "given": "Lilit", "initials": "L"}, {"family": "Sundsfjord", "given": "Arnfinn", "initials": "A"}, {"family": "Hegstad", "given": "Kristin", "initials": "K", "orcid": "0000-0002-1314-0497", "researcher": {"href": "https://publications.scilifelab.se/researcher/36ba3d809302499593f4a315ae867e1e.json"}}, {"family": "Atkinson", "given": "Gemma C", "initials": "GC"}, {"family": "Pelechano", "given": "Vicent", "initials": "V", "orcid": "0000-0002-9415-788X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e906e11225514a289df84a2145f807fe.json"}}, {"family": "Wilson", "given": "Daniel N", "initials": "DN", "orcid": "0000-0003-3816-3828", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd50ba35f7c74d7e9d4f42fbc49739f2.json"}}, {"family": "Hauryliuk", "given": "Vasili", "initials": "V", "orcid": "0000-0003-2389-5057", "researcher": {"href": "https://publications.scilifelab.se/researcher/17ea83b1d20f43f9872edbf89b275e5d.json"}}], "type": "journal article", "published": "2022-04-06", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "13", "issue": "1", "pages": "1860", "issn-l": "2041-1723"}, "abstract": "PoxtA and OptrA are ATP binding cassette (ABC) proteins of the F subtype (ABCF). They confer resistance to oxazolidinone and phenicol antibiotics, such as linezolid and chloramphenicol, which stall translating ribosomes when certain amino acids are present at a defined position in the nascent polypeptide chain. These proteins are often encoded on mobile genetic elements, facilitating their rapid spread amongst Gram-positive bacteria, and are thought to confer resistance by binding to the ribosome and dislodging the bound antibiotic. However, the mechanistic basis of this resistance remains unclear. Here we refine the PoxtA spectrum of action, demonstrate alleviation of linezolid-induced context-dependent translational stalling, and present cryo-electron microscopy structures of PoxtA in complex with the Enterococcus faecalis 70S ribosome. PoxtA perturbs the CCA-end of the P-site tRNA, causing it to shift by \u223c4 \u00c5 out of the ribosome, corresponding to a register shift of approximately one amino acid for an attached nascent polypeptide chain. We postulate that the perturbation of the P-site tRNA by PoxtA thereby alters the conformation of the attached nascent chain to disrupt the drug binding site.", "doi": "10.1038/s41467-022-29274-9", "pmid": "35387982", "labels": {"Cryo-EM": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8987054"}, {"db": "pii", "key": "10.1038/s41467-022-29274-9"}], "notes": [], "created": "2022-11-09T15:58:01.251Z", "modified": "2024-01-16T13:48:37.095Z"}, {"entity": "publication", "iuid": "430c270305eb49f3a5e61581718ae6c7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/430c270305eb49f3a5e61581718ae6c7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/430c270305eb49f3a5e61581718ae6c7"}}, "title": "RqcH and RqcP catalyze processive poly-alanine synthesis in a reconstituted ribosome-associated quality control system.", "authors": [{"family": "Takada", "given": "Hiraku", "initials": "H"}, {"family": "Crowe-McAuliffe", "given": "Caillan", "initials": "C"}, {"family": "Polte", "given": "Christine", "initials": "C"}, {"family": "Sidorova", "given": "Zhanna Yu", "initials": "ZY"}, {"family": "Murina", "given": "Victoriia", "initials": "V"}, {"family": "Atkinson", "given": "Gemma C", "initials": "GC"}, {"family": "Konevega", "given": "Andrey L", "initials": "AL"}, {"family": "Ignatova", "given": "Zoya", "initials": "Z", "orcid": "0000-0002-9478-8825", "researcher": {"href": "https://publications.scilifelab.se/researcher/15d0b4be02ca4c1884f0ad793462901c.json"}}, {"family": "Wilson", "given": "Daniel N", "initials": "DN", "orcid": "0000-0003-3816-3828", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd50ba35f7c74d7e9d4f42fbc49739f2.json"}}, {"family": "Hauryliuk", "given": "Vasili", "initials": "V", "orcid": "0000-0003-2389-5057", "researcher": {"href": "https://publications.scilifelab.se/researcher/17ea83b1d20f43f9872edbf89b275e5d.json"}}], "type": "journal article", "published": "2021-08-20", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "issn-l": "0305-1048", "volume": "49", "issue": "14", "pages": "8355-8369"}, "abstract": "In the cell, stalled ribosomes are rescued through ribosome-associated protein quality-control (RQC) pathways. After splitting of the stalled ribosome, a C-terminal polyalanine 'tail' is added to the unfinished polypeptide attached to the tRNA on the 50S ribosomal subunit. In Bacillus subtilis, polyalanine tailing is catalyzed by the NEMF family protein RqcH, in cooperation with RqcP. However, the mechanistic details of this process remain unclear. Here we demonstrate that RqcH is responsible for tRNAAla selection during RQC elongation, whereas RqcP lacks any tRNA specificity. The ribosomal protein uL11 is crucial for RqcH, but not RqcP, recruitment to the 50S subunit, and B. subtilis lacking uL11 are RQC-deficient. Through mutational mapping, we identify critical residues within RqcH and RqcP that are important for interaction with the P-site tRNA and/or the 50S subunit. Additionally, we have reconstituted polyalanine-tailing in vitro and can demonstrate that RqcH and RqcP are necessary and sufficient for processivity in a minimal system. Moreover, the in vitro reconstituted system recapitulates our in vivo findings by reproducing the importance of conserved residues of RqcH and RqcP for functionality. Collectively, our findings provide mechanistic insight into the role of RqcH and RqcP in the bacterial RQC pathway.", "doi": "10.1093/nar/gkab589", "pmid": "34255840", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "6320412"}, {"db": "pmc", "key": "PMC8373112"}], "notes": [], "created": "2021-12-14T12:41:03.729Z", "modified": "2022-04-01T07:14:15.200Z"}, {"entity": "publication", "iuid": "9db452ca3ba2471fadd10ad1333ec980", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9db452ca3ba2471fadd10ad1333ec980.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9db452ca3ba2471fadd10ad1333ec980"}}, "title": "Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens.", "authors": [{"family": "Crowe-McAuliffe", "given": "Caillan", "initials": "C"}, {"family": "Murina", "given": "Victoriia", "initials": "V", "orcid": "0000-0003-1523-1816", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb97467a29cb494baa858f2a9c5287c8.json"}}, {"family": "Turnbull", "given": "Kathryn Jane", "initials": "KJ"}, {"family": "Kasari", "given": "Marje", "initials": "M"}, {"family": "Mohamad", "given": "Merianne", "initials": "M"}, {"family": "Polte", "given": "Christine", "initials": "C"}, {"family": "Takada", "given": "Hiraku", "initials": "H", "orcid": "0000-0003-2034-5666", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d9dfa63a3004266bc782f77263dcc9e.json"}}, {"family": "Vaitkevicius", "given": "Karolis", "initials": "K"}, {"family": "Johansson", "given": "J\u00f6rgen", "initials": "J"}, {"family": "Ignatova", "given": "Zoya", "initials": "Z"}, {"family": "Atkinson", "given": "Gemma C", "initials": "GC", "orcid": "0000-0002-4861-4584", "researcher": {"href": "https://publications.scilifelab.se/researcher/d810a2d001a74ccda5b376198896cbf6.json"}}, {"family": "O'Neill", "given": "Alex J", "initials": "AJ"}, {"family": "Hauryliuk", "given": "Vasili", "initials": "V", "orcid": "0000-0003-2389-5057", "researcher": {"href": "https://publications.scilifelab.se/researcher/17ea83b1d20f43f9872edbf89b275e5d.json"}}, {"family": "Wilson", "given": "Daniel N", "initials": "DN", "orcid": "0000-0003-3816-3828", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd50ba35f7c74d7e9d4f42fbc49739f2.json"}}], "type": "journal article", "published": "2021-06-11", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "12", "issue": "1", "pages": "3577", "issn-l": "2041-1723"}, "abstract": "Target protection proteins confer resistance to the host organism by directly binding to the antibiotic target. One class of such proteins are the antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F-subtype (ARE-ABCFs), which are widely distributed throughout Gram-positive bacteria and bind the ribosome to alleviate translational inhibition from antibiotics that target the large ribosomal subunit. Here, we present single-particle cryo-EM structures of ARE-ABCF-ribosome complexes from three Gram-positive pathogens: Enterococcus faecalis LsaA, Staphylococcus haemolyticus VgaALC and Listeria monocytogenes VgaL. Supported by extensive mutagenesis analysis, these structures enable a general model for antibiotic resistance mediated by these ARE-ABCFs to be proposed. In this model, ABCF binding to the antibiotic-stalled ribosome mediates antibiotic release via mechanistically diverse long-range conformational relays that converge on a few conserved ribosomal RNA nucleotides located at the peptidyltransferase center. These insights are important for the future development of antibiotics that overcome such target protection resistance mechanisms.", "doi": "10.1038/s41467-021-23753-1", "pmid": "34117249", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-021-23753-1"}, {"db": "pmc", "key": "PMC8196190"}], "notes": [], "created": "2021-12-14T12:35:33.249Z", "modified": "2021-12-14T12:35:33.401Z"}, {"entity": "publication", "iuid": "2ba033fd1efc4e399b47b8681da72993", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2ba033fd1efc4e399b47b8681da72993.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2ba033fd1efc4e399b47b8681da72993"}}, "title": "Structural Basis for Bacterial Ribosome-Associated Quality Control by RqcH and RqcP.", "authors": [{"family": "Crowe-McAuliffe", "given": "Caillan", "initials": "C"}, {"family": "Takada", "given": "Hiraku", "initials": "H"}, {"family": "Murina", "given": "Victoriia", "initials": "V"}, {"family": "Polte", "given": "Christine", "initials": "C"}, {"family": "Kasvandik", "given": "Sergo", "initials": "S"}, {"family": "Tenson", "given": "Tanel", "initials": "T"}, {"family": "Ignatova", "given": "Zoya", "initials": "Z", "orcid": "0000-0002-9478-8825", "researcher": {"href": "https://publications.scilifelab.se/researcher/15d0b4be02ca4c1884f0ad793462901c.json"}}, {"family": "Atkinson", "given": "Gemma C", "initials": "GC"}, {"family": "Wilson", "given": "Daniel N", "initials": "DN", "orcid": "0000-0003-3816-3828", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd50ba35f7c74d7e9d4f42fbc49739f2.json"}}, {"family": "Hauryliuk", "given": "Vasili", "initials": "V", "orcid": "0000-0003-2389-5057", "researcher": {"href": "https://publications.scilifelab.se/researcher/17ea83b1d20f43f9872edbf89b275e5d.json"}}], "type": "journal article", "published": "2021-01-07", "journal": {"title": "Mol. Cell", "issn": "1097-4164", "issn-l": "1097-2765", "volume": "81", "issue": "1", "pages": "115-126.e7"}, "abstract": "In all branches of life, stalled translation intermediates are recognized and processed by ribosome-associated quality control (RQC) pathways. RQC begins with the splitting of stalled ribosomes, leaving an unfinished polypeptide still attached to the large subunit. Ancient and conserved NEMF family RQC proteins target these incomplete proteins for degradation by the addition of C-terminal \"tails.\" How such tailing can occur without the regular suite of translational components is, however, unclear. Using single-particle cryo-electron microscopy (EM) of native complexes, we show that C-terminal tailing in Bacillus subtilis is mediated by NEMF protein RqcH in concert with RqcP, an Hsp15 family protein. Our structures reveal how these factors mediate tRNA movement across the ribosomal 50S subunit to synthesize polypeptides in the absence of mRNA or the small subunit.", "doi": "10.1016/j.molcel.2020.11.002", "pmid": "33259810", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "S1097-2765(20)30780-2"}], "notes": [], "created": "2020-12-10T11:26:33.440Z", "modified": "2021-11-10T12:27:47.555Z"}]}