{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:40:07Z","timestamp":1762252807530,"version":"3.41.2"},"reference-count":51,"publisher":"Portland Press Ltd.","issue":"5","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":321,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,31]]},"abstract":"<jats:p>Cholera toxin (CT) is composed of a disulfide-linked A1\/A2 heterodimer and a ring-like, cell-binding B homopentamer. The catalytic A1 subunit must dissociate from CTA2\/CTB5 to manifest its cellular activity. Reduction of the A1\/A2 disulfide bond is required for holotoxin disassembly, but reduced CTA1 does not spontaneously separate from CTA2\/CTB5: protein disulfide isomerase (PDI) is responsible for displacing CTA1 from its non-covalent assembly in the CT holotoxin. Contact with PDI shifts CTA1 from a protease-resistant conformation to a protease-sensitive conformation, which is thought to represent the PDI-mediated unfolding of CTA1. Based solely on this finding, PDI is widely viewed as an \u2018unfoldase\u2019 that triggers toxin disassembly by unfolding the holotoxin-associated A1 subunit. In contrast with this unfoldase model of PDI function, we report the ability of PDI to render CTA1 protease-sensitive is unrelated to its role in toxin disassembly. Multiple conditions that promoted PDI-induced protease sensitivity in CTA1 did not support PDI-mediated disassembly of the CT holotoxin. Moreover, preventing the PDI-induced shift in CTA1 protease sensitivity did not affect PDI-mediated disassembly of the CT holotoxin. Denatured PDI could still convert CTA1 into a protease-sensitive state, and equal or excess molar fractions of PDI were required for both efficient conversion of CTA1 into a protease-sensitive state and efficient disassembly of the CT holotoxin. These observations indicate the \u2018unfoldase\u2019 property of PDI does not play a functional role in CT disassembly and does not represent an enzymatic activity.<\/jats:p>","DOI":"10.1042\/bsr20181320","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T16:35:22Z","timestamp":1534955722000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Protein disulfide isomerase does not act as an unfoldase in the disassembly of cholera toxin"],"prefix":"10.1042","volume":"38","author":[{"given":"Patrick","family":"Cherubin","sequence":"first","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Guyette","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Taylor","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Herndon","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Burress","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aladdin","family":"Riad","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suren\u00a0A.","family":"Tatulian","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Central Florida, Orlando, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Teter","sequence":"additional","affiliation":[{"name":"Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2018,9,7]]},"reference":[{"key":"2021111619135517300_B1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1089\/ars.2012.4630","article-title":"Structural insights into the redox-regulated dynamic conformations of human protein disulfide isomerase","volume":"19","author":"Wang","year":"2013","journal-title":"Antioxid. 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