{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:27:00Z","timestamp":1774315620852,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010190","name":"GENCI","doi-asserted-by":"publisher","award":["A0080710764"],"award-info":[{"award-number":["A0080710764"]}],"id":[{"id":"10.13039\/501100010190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010190","name":"GENCI","doi-asserted-by":"publisher","award":["FFR-Cottone"],"award-info":[{"award-number":["FFR-Cottone"]}],"id":[{"id":"10.13039\/501100010190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CNRS","award":["A0080710764"],"award-info":[{"award-number":["A0080710764"]}]},{"name":"CNRS","award":["FFR-Cottone"],"award-info":[{"award-number":["FFR-Cottone"]}]},{"name":"University of Lorraine","award":["A0080710764"],"award-info":[{"award-number":["A0080710764"]}]},{"name":"University of Lorraine","award":["FFR-Cottone"],"award-info":[{"award-number":["FFR-Cottone"]}]},{"DOI":"10.13039\/501100004913","name":"University of Palermo","doi-asserted-by":"publisher","award":["A0080710764"],"award-info":[{"award-number":["A0080710764"]}],"id":[{"id":"10.13039\/501100004913","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004913","name":"University of Palermo","doi-asserted-by":"publisher","award":["FFR-Cottone"],"award-info":[{"award-number":["FFR-Cottone"]}],"id":[{"id":"10.13039\/501100004913","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The toxicity of botulinum multi-domain neurotoxins (BoNTs) arises from a sequence of molecular events, in which the translocation of the catalytic domain through the membrane of a neurotransmitter vesicle plays a key role. A recent structural study of the translocation domain of BoNTs suggests that the interaction with the membrane is driven by the transition of an \u03b1 helical switch towards a \u03b2 hairpin. Atomistic simulations in conjunction with the mesoscopic Twister model are used to investigate the consequences of this proposition for the toxin\u2013membrane interaction. The conformational mobilities of the domain, as well as the effect of the membrane, implicitly examined by comparing water and water\u2013ethanol solvents, lead to the conclusion that the transition of the switch modifies the internal dynamics and the effect of membrane hydrophobicity on the whole protein. The central two \u03b1 helices, helix 1 and helix 2, forming two coiled-coil motifs, are analyzed using the Twister model, in which the initial deformation of the membrane by the protein is caused by the presence of local torques arising from asymmetric positions of hydrophobic residues. Different torque distributions are observed depending on the switch conformations and permit an origin for the mechanism opening the membrane to be proposed.<\/jats:p>","DOI":"10.3390\/ijms25052481","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T11:50:07Z","timestamp":1708429807000},"page":"2481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Conformational Space of the Translocation Domain of Botulinum Toxin: Atomistic Modeling and Mesoscopic Description of the Coiled-Coil Helix Bundle"],"prefix":"10.3390","volume":"25","author":[{"given":"Alexandre","family":"Delort","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lorraine, CNRS, LPCT, 57000 Metz, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6923-6394","authenticated-orcid":false,"given":"Grazia","family":"Cottone","sequence":"additional","affiliation":[{"name":"Department of Physics and Chemistry-Emilio Segr\u00e9, University of Palermo, 90128 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3276-3366","authenticated-orcid":false,"given":"Th\u00e9r\u00e8se E.","family":"Malliavin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, CNRS, LPCT, 54000 Nancy, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6062-8073","authenticated-orcid":false,"given":"Martin Michael","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, CNRS, LPCT, 57000 Metz, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1146\/annurev-biochem-013118-111654","article-title":"Botulinum and Tetanus Neurotoxins","volume":"88","author":"Dong","year":"2019","journal-title":"Annu. 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