{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:25:49Z","timestamp":1760228749061,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T00:00:00Z","timestamp":1652918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a joint postgraduate studentship between University of Bath and Ipsen Bioinnovation Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum neurotoxins (BoNT) are a group of clostridial toxins that cause the potentially fatal neuroparalytic disease botulism. Although highly toxic, BoNTs are utilized as therapeutics to treat a range of neuromuscular conditions. Several serotypes (BoNT\/A-\/G, \/X) have been identified with vastly differing toxicological profiles. Each serotype can be further sub-categorised into subtypes due to subtle variations in their protein sequence. These minor changes have been attributed to differences in both the duration of action and potency for BoNT\/A subtypes. BoNTs are composed of three domains\u2014a cell-binding domain, a translocation domain, and a catalytic domain. In this paper, we present the crystal structures of the botulinum neurotoxin A2 cell binding domain, both alone and in complex with its receptor ganglioside GD1a at 1.63 and 2.10 \u00c5, respectively. The analysis of these structures reveals a potential redox-dependent Lys-O-Cys bridge close to the ganglioside binding site and a hinge motion between the HCN and HCC subdomains. Furthermore, we make a detailed comparison with the previously reported HC\/A2:SV2C structure for a comprehensive structural analysis of HC\/A2 receptor binding.<\/jats:p>","DOI":"10.3390\/toxins14050356","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:18:11Z","timestamp":1653005891000},"page":"356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Structural Features of Clostridium botulinum Neurotoxin Subtype A2 Cell Binding Domain"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-4283","authenticated-orcid":false,"given":"Kyle S.","family":"Gregory","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9250-4166","authenticated-orcid":false,"given":"Tejaswini B.","family":"Mahadeva","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6359-0229","authenticated-orcid":false,"given":"Sai Man","family":"Liu","sequence":"additional","affiliation":[{"name":"Protein Sciences Department, Ipsen Bioinnovation Limited, 102 Park Drive, Milton Park, Abingdon OX14 4RY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-4058","authenticated-orcid":false,"given":"K. Ravi","family":"Acharya","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1007\/s11910-010-0129-z","article-title":"An update on the neurologic applications of botulinum toxins","volume":"10","author":"Evidente","year":"2010","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/978-3-642-61105-6_32","article-title":"The mechanism of action of tetanus and botulinum neurotoxins","volume":"18","author":"Monteucucco","year":"1996","journal-title":"Arch. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Webb, R.P. (2018). Engineering of botulinum neurotoxins for biomedical applications. 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