{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:15:10Z","timestamp":1782900910814,"version":"3.54.5"},"reference-count":64,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"35","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8,29]]},"abstract":"<jats:p>Botulinum neurotoxin serotype B1 (BoNT\/B) is a highly potent neurotoxin and therapeutic agent. Here, we present the structure of the complete 14-subunit (780 kDa) progenitor toxin complex (L-PTC) and of five subcomplexes. The structures show how the toxin interacts with its associated components in their role to protect and deliver BoNT\/B across epithelial barriers. Each subcomplex, including the M-PTC, M-PTC\u2013HA70, NTNH-HA70, and HA70 trimer, provides detailed understanding of the assembly mechanism, in which the NTNH-nLoop adopts a unique fold that locks the M-PTC into a central pore formed by HA70. The HA subcomplex presents a tripod architecture with flexible legs that may adapt to the rugged cell surface. Mass photometry reveals the pH dependence of BoNT\/B release from the complex which is unexpectedly influenced by the presence of HA70. This study provides the complete L-PTC structure, offering insights into its assemblage and supporting the development of countermeasures and therapeutic applications.<\/jats:p>","DOI":"10.1126\/sciadv.adx5058","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T17:59:06Z","timestamp":1756317546000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Structure of the complete 14-subunit botulinum neurotoxin B complex reveals a unique anchoring through the narrow central pore of HA70"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5842-8527","authenticated-orcid":true,"given":"Ajda","family":"Kr\u010d","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7893-0249","authenticated-orcid":true,"given":"Sara Persson","family":"Ko\u0161enina","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2592-2442","authenticated-orcid":true,"given":"Maria B.","family":"Nowakowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-2310","authenticated-orcid":true,"given":"Geoffrey","family":"Masuyer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-3417","authenticated-orcid":true,"given":"P\u00e5l","family":"Stenmark","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3295"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-013118-111654"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02131-14"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-024-03828-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.44.101802.121554"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.051908.125345"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.06093.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703619200"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1380-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.1997.00313.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1253823"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214270"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep17795"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42004-024-01262-8"},{"key":"e_1_3_2_16_2","unstructured":"M. B. Nowakowska \u201cThe Role of OrfX and P47 Proteins in Oral Toxicity of Botulinum Neurotoxin \u201c thesis University of Helsinki Helsinki Finland (2024)."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10732-w"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.12.018"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","unstructured":"X. Wei B. Lobb K. Wang M. Dong A. C. 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