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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,1,14]]},"abstract":"<jats:p>\n                    Targeting\n                    <jats:italic>Clostridium difficile<\/jats:italic>\n                    infection is challenging because treatment options are limited, and high recurrence rates are common. One reason for this is that hypervirulent\n                    <jats:italic>C. difficile<\/jats:italic>\n                    strains often have a binary toxin termed the\n                    <jats:italic>C. difficile<\/jats:italic>\n                    toxin, in addition to the enterotoxins TsdA and TsdB. The\n                    <jats:italic>C. difficile<\/jats:italic>\n                    toxin has an enzymatic component, termed CDTa, and a pore-forming or delivery subunit termed CDTb. CDTb was characterized here using a combination of single-particle cryoelectron microscopy, X-ray crystallography, NMR, and other biophysical methods. In the absence of CDTa, 2 di-heptamer structures for activated CDTb (1.0 MDa) were solved at atomic resolution, including a symmetric (\n                    <jats:sup>Sym<\/jats:sup>\n                    CDTb; 3.14 \u00c5) and an asymmetric form (\n                    <jats:sup>Asym<\/jats:sup>\n                    CDTb; 2.84 \u00c5). Roles played by 2 receptor-binding domains of activated CDTb were of particular interest since the receptor-binding domain 1 lacks sequence homology to any other known toxin, and the receptor-binding domain 2 is completely absent in other well-studied heptameric toxins (i.e., anthrax). For\n                    <jats:sup>Asym<\/jats:sup>\n                    CDTb, a Ca\n                    <jats:sup>2+<\/jats:sup>\n                    binding site was discovered in the first receptor-binding domain that is important for its stability, and the second receptor-binding domain was found to be critical for host cell toxicity and the di-heptamer fold for both forms of activated CDTb. Together, these studies represent a starting point for developing structure-based drug-design strategies to target the most severe strains of\n                    <jats:italic>C. difficile<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.1919490117","type":"journal-article","created":{"date-parts":[[2020,1,2]],"date-time":"2020-01-02T20:05:55Z","timestamp":1577995555000},"page":"1049-1058","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":38,"title":["Structure of the cell-binding component of the\n                    <i>Clostridium difficile<\/i>\n                    binary toxin reveals a di-heptamer macromolecular assembly"],"prefix":"10.1073","volume":"117","author":[{"given":"Xingjian","family":"Xu","sequence":"first","affiliation":[{"name":"City University of New York Advanced Science Research Center, City University of New York, New York, NY 10017;"},{"name":"PhD Program in Biochemistry, The Graduate Center, City University of New York, New York, NY 10017;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Godoy-Ruiz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; 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