{"entity": "researcher", "timestamp": "2026-08-15T07:19:03.627Z", "family": "Mart\u00ednez-Carranza", "given": "Markel", "initials": "M", "orcid": "0000-0003-0192-9762", "affiliations": ["Department of Biochemistry and Biophysics, Stockholm University, SE-10691, Stockholm, Sweden.", "Department of Experimental Medical Science, Lund University, Box 118, SE-22100, Lund, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/0ad7db8205c847a5bf56843d600e5ce1.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/0ad7db8205c847a5bf56843d600e5ce1"}}, "publications": [{"entity": "publication", "iuid": "1d08fde7b77e4bf5b87eac8ed9144e1c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d08fde7b77e4bf5b87eac8ed9144e1c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d08fde7b77e4bf5b87eac8ed9144e1c"}}, "title": "Activity of botulinum neurotoxin X and its structure when shielded by a non-toxic non-hemagglutinin protein.", "authors": [{"family": "Mart\u00ednez-Carranza", "given": "Markel", "initials": "M", "orcid": "0000-0003-0192-9762", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ad7db8205c847a5bf56843d600e5ce1.json"}}, {"family": "\u0160kerlov\u00e1", "given": "Jana", "initials": "J", "orcid": "0000-0002-9579-4047", "researcher": {"href": "https://publications.scilifelab.se/researcher/cde5c1c6ccb94ca3be0b092771e67524.json"}}, {"family": "Lee", "given": "Pyung-Gang", "initials": "PG"}, {"family": "Zhang", "given": "Jie", "initials": "J"}, {"family": "Kr\u010d", "given": "Ajda", "initials": "A", "orcid": "0009-0007-5842-8527", "researcher": {"href": "https://publications.scilifelab.se/researcher/cda5c360c20149279692c5d69df7a694.json"}}, {"family": "Sirohiwal", "given": "Abhishek", "initials": "A", "orcid": "0000-0002-4073-7627", "researcher": {"href": "https://publications.scilifelab.se/researcher/5171ae67d7bc4979908b2c12ecf1ce75.json"}}, {"family": "Burgin", "given": "Dave", "initials": "D"}, {"family": "Elliott", "given": "Mark", "initials": "M"}, {"family": "Philippe", "given": "Jules", "initials": "J"}, {"family": "Donald", "given": "Sarah", "initials": "S"}, {"family": "Hornby", "given": "Fraser", "initials": "F"}, {"family": "Henriksson", "given": "Linda", "initials": "L"}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications.scilifelab.se/researcher/41dcc0806dba4a56bb04725812f3a000.json"}}, {"family": "Kaila", "given": "Ville R I", "initials": "VRI", "orcid": "0000-0003-4464-6324", "researcher": {"href": "https://publications.scilifelab.se/researcher/cdcc63256cea406c9cb9cdaecc9cbcbe.json"}}, {"family": "Beard", "given": "Matthew", "initials": "M"}, {"family": "Dong", "given": "Min", "initials": "M", "orcid": "0000-0002-1744-7293", "researcher": {"href": "https://publications.scilifelab.se/researcher/30fd6ee44bfd4ae38eb733e19cbf338c.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}], "type": "journal article", "published": "2024-08-13", "journal": {"title": "Commun Chem", "issn": "2399-3669", "volume": "7", "issue": "1", "pages": "179", "issn-l": null}, "abstract": "Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein (NTNH) with which they form a 300 kDa complex, to resist acidic and proteolytic attack from the digestive tract. We have previously identified a new botulinum neurotoxin serotype, BoNT/X, that has unique and therapeutically attractive properties. We present the cryo-EM structure of the BoNT/X-NTNH/X complex and the crystal structure of the isolated NTNH protein. Unexpectedly, the BoNT/X complex is stable and protease-resistant at both neutral and acidic pH and disassembles only in alkaline conditions. Using the stabilizing effect of NTNH, we isolated BoNT/X and showed that it has very low potency both in vitro and in vivo. Given the high catalytic activity and translocation efficacy of BoNT/X, low activity of the full toxin is likely due to the receptor-binding domain, which presents very weak ganglioside binding and exposed hydrophobic surfaces.", "doi": "10.1038/s42004-024-01262-8", "pmid": "39138288", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11322297"}, {"db": "pii", "key": "10.1038/s42004-024-01262-8"}], "notes": [], "created": "2024-11-15T13:45:47.397Z", "modified": "2025-10-25T10:17:13.297Z"}, {"entity": "publication", "iuid": "7da5a92f39cc4ce2a269162f66b0d2e7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7da5a92f39cc4ce2a269162f66b0d2e7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7da5a92f39cc4ce2a269162f66b0d2e7"}}, "title": "A nucleotide-sensing oligomerization mechanism that controls NrdR-dependent transcription of ribonucleotide reductases.", "authors": [{"family": "Rozman Grinberg", "given": "Inna", "initials": "I", "orcid": "0000-0003-3094-1998", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d4a64db2f9544b2bde744b063dc5247.json"}}, {"family": "Mart\u00ednez-Carranza", "given": "Markel", "initials": "M", "orcid": "0000-0003-0192-9762", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ad7db8205c847a5bf56843d600e5ce1.json"}}, {"family": "Bimai", "given": "Ornella", "initials": "O", "orcid": "0000-0003-0562-7251", "researcher": {"href": "https://publications.scilifelab.se/researcher/9545ade4d51c4c4089d97eb74841deec.json"}}, {"family": "Noua\u00efria", "given": "Ghada", "initials": "G"}, {"family": "Shahid", "given": "Saher", "initials": "S"}, {"family": "Lundin", "given": "Daniel", "initials": "D", "orcid": "0000-0002-8779-6464", "researcher": {"href": "https://publications.scilifelab.se/researcher/227cc90e084348a193fee05eb23a6bf3.json"}}, {"family": "Logan", "given": "Derek T", "initials": "DT", "orcid": "0000-0002-0098-8560", "researcher": {"href": "https://publications.scilifelab.se/researcher/da2734243cdb4142be696e5a82e788ae.json"}}, {"family": "Sj\u00f6berg", "given": "Britt-Marie", "initials": "BM", "orcid": "0000-0001-5953-3360", "researcher": {"href": "https://publications.scilifelab.se/researcher/fab276f213364c2eaa6fe3dc5c9b01ff.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}], "type": "journal article", "published": "2022-05-16", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "13", "issue": "1", "pages": "2700", "issn-l": "2041-1723"}, "abstract": "Ribonucleotide reductase (RNR) is an essential enzyme that catalyzes the synthesis of DNA building blocks in virtually all living cells. NrdR, an RNR-specific repressor, controls the transcription of RNR genes and, often, its own, in most bacteria and some archaea. NrdR senses the concentration of nucleotides through its ATP-cone, an evolutionarily mobile domain that also regulates the enzymatic activity of many RNRs, while a Zn-ribbon domain mediates binding to NrdR boxes upstream of and overlapping the transcription start site of RNR genes. Here, we combine biochemical and cryo-EM studies of NrdR from Streptomyces coelicolor to show, at atomic resolution, how NrdR binds to DNA. The suggested mechanism involves an initial dodecamer loaded with two ATP molecules that cannot bind to DNA. When dATP concentrations increase, an octamer forms that is loaded with one molecule each of dATP and ATP per monomer. A tetramer derived from this octamer then binds to DNA and represses transcription of RNR. In many bacteria - including well-known pathogens such as Mycobacterium tuberculosis - NrdR simultaneously controls multiple RNRs and hence DNA synthesis, making it an excellent target for novel antibiotics development.", "doi": "10.1038/s41467-022-30328-1", "pmid": "35577776", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-022-30328-1"}, {"db": "pmc", "key": "PMC9110341"}], "notes": [], "created": "2022-05-30T08:19:29.322Z", "modified": "2023-12-04T10:19:23.813Z"}, {"entity": "publication", "iuid": "1d9cf52bf48f4013b24383a715361632", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d9cf52bf48f4013b24383a715361632.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d9cf52bf48f4013b24383a715361632"}}, "title": "Structural Analysis of Botulinum Neurotoxins Type B and E by Cryo-EM.", "authors": [{"family": "Ko\u0161enina", "given": "Sara", "initials": "S", "orcid": "0000-0001-7893-0249", "researcher": {"href": "https://publications.scilifelab.se/researcher/9370d4ecf19c438bb205c43c23f94f26.json"}}, {"family": "Mart\u00ednez-Carranza", "given": "Markel", "initials": "M", "orcid": "0000-0003-0192-9762", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ad7db8205c847a5bf56843d600e5ce1.json"}}, {"family": "Davies", "given": "Jonathan R", "initials": "JR"}, {"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications.scilifelab.se/researcher/41dcc0806dba4a56bb04725812f3a000.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}], "type": "journal article", "published": "2021-12-23", "journal": {"title": "Toxins (Basel)", "issn": "2072-6651", "volume": "14", "issue": "1", "issn-l": "2072-6651"}, "abstract": "Botulinum neurotoxins (BoNTs) are the causative agents of a potentially lethal paralytic disease targeting cholinergic nerve terminals. Multiple BoNT serotypes exist, with types A, B and E being the main cause of human botulism. Their extreme toxicity has been exploited for cosmetic and therapeutic uses to treat a wide range of neuromuscular disorders. Although naturally occurring BoNT types share a common end effect, their activity varies significantly based on the neuronal cell-surface receptors and intracellular SNARE substrates they target. These properties are the result of structural variations that have traditionally been studied using biophysical methods such as X-ray crystallography. Here, we determined the first structures of botulinum neurotoxins using single-particle cryogenic electron microscopy. The maps obtained at 3.6 and 3.7 \u00c5 for BoNT/B and /E, respectively, highlight the subtle structural dynamism between domains, and of the binding domain in particular. This study demonstrates how the recent advances made in the field of single-particle electron microscopy can be applied to bacterial toxins of clinical relevance and the botulinum neurotoxin family in particular.", "doi": "10.3390/toxins14010014", "pmid": "35050991", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8781748"}, {"db": "pii", "key": "toxins14010014"}], "notes": [], "created": "2022-03-22T10:00:44.051Z", "modified": "2023-12-04T10:18:39.303Z"}]}