{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:17:07Z","timestamp":1792675027786,"version":"4.5.0"},"reference-count":47,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,4,2]]},"abstract":"<jats:p>\n                    Botulinum neurotoxin (BoNT) is produced by\n                    <jats:italic>Clostridium botulinum<\/jats:italic>\n                    and associates with nontoxic neurotoxin-associated proteins to form high-molecular weight progenitor complexes (PCs). The PCs are required for the oral toxicity of BoNT in the context of food-borne botulism and are thought to protect BoNT from destruction in the gastrointestinal tract and aid in absorption from the gut lumen. The PC can differ in size and protein content depending on the\n                    <jats:italic>C. botulinum<\/jats:italic>\n                    strain. The oral toxicity of the BoNT PC increases as the size of the PC increases, but the molecular architecture of these large complexes and how they contribute to BoNT toxicity have not been elucidated. We have generated 2D images of PCs from strains producing BoNT serotypes A1, B, and E using negative stain electron microscopy and single-particle averaging. The BoNT\/A1 and BoNT\/B PCs were observed as ovoid-shaped bodies with three appendages, whereas the BoNT\/E PC was observed as an ovoid body. Both the BoNT\/A1 and BoNT\/B PCs showed significant flexibility, and the BoNT\/B PC was documented as a heterogeneous population of assembly\/disassembly intermediates. We have also determined 3D structures for each serotype using the random conical tilt approach. Crystal structures of the individual proteins were placed into the BoNT\/A1 and BoNT\/B PC electron density maps to generate unique detailed models of the BoNT PCs. The structures highlight an effective platform that can be engineered for the development of mucosal vaccines and the intestinal absorption of oral biologics.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1222139110","type":"journal-article","created":{"date-parts":[[2013,3,19]],"date-time":"2013-03-19T03:06:17Z","timestamp":1363662377000},"page":"5630-5635","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":82,"title":["Molecular assembly of botulinum neurotoxin progenitor complexes"],"prefix":"10.1073","volume":"110","author":[{"given":"Desir\u00e9e A.","family":"Benefield","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott K.","family":"Dessain","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research, Wynnewood, PA 19096;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Shine","sequence":"additional","affiliation":[{"name":"List Biological Laboratories, Campbell, CA 95008; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie D.","family":"Ohi","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Borden","family":"Lacy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville TN 37232;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,3,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2911(09)05503-9"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583500003292"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/2338"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb26614.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012595020-6\/50009-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.44.101802.121554"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(82)90061-4"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anaerobe.2004.01.001"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.16.1.107-109.1977"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.28.2.303-309.1980"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.7883\/yoken1952.27.241"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1214270"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.34.21950"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.3.1147-1154.2003"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-143-12-3841"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.04.183"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2005.11.014"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01147-9"},{"key":"e_1_3_3_19_2","first-page":"355","article-title":"The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption","volume":"10","author":"Matsumura T","year":"2008","unstructured":"T Matsumura, et al., The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption. 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