{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:49:26Z","timestamp":1760150966579,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Botulinum neurotoxins (BoNT) cause the potentially fatal neuroparalytic disease botulism that arises due to proteolysis of a SNARE protein. Each BoNT is comprised of three domains: a cell binding domain (HC), a translocation domain (HN), and a catalytic (Zn2+ endopeptidase) domain (LC). The HC is responsible for neuronal specificity by targeting both a protein and ganglioside receptor at the neuromuscular junction. Although highly toxic, some BoNTs are commercially available as therapeutics for the treatment of a range of neuromuscular conditions. Here we present the crystal structures of two BoNT cell binding domains, HC\/A4 and HC\/A5, in a complex with the oligosaccharide of ganglioside, GD1a and GM1b, respectively. These structures, along with a detailed comparison with the previously reported apo-structures, reveal the conformational changes that occur upon ganglioside binding and the interactions involved.<\/jats:p>","DOI":"10.3390\/toxins14020129","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T23:42:20Z","timestamp":1644363740000},"page":"129","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Crystal Structures of Botulinum Neurotoxin Subtypes A4 and A5 Cell Binding Domains in Complex with Receptor Ganglioside"],"prefix":"10.3390","volume":"14","author":[{"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"}]},{"given":"Otsile O.","family":"Mojanaga","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":[[2022,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1128\/CMR.3.1.66","article-title":"Toxigenic clostridia","volume":"3","author":"Hatheway","year":"1990","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1128\/mr.46.1.86-94.1982","article-title":"Bacterial toxins: A table of lethal amounts","volume":"46","author":"Gill","year":"1982","journal-title":"Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Fonfria, E., Maignel, J., Lezmi, S., Martin, V., Splevins, A., Shubber, S., Kalinichev, M., Foster, K., Picaut, P., and Krupp, J. (2018). 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