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It has been proposed that the underlying mechanism for transport by ASBT is an elevator-style alternating-access model, which was deduced mainly by comparing high-resolution structures of two bacterial ASBT homologs (ASBT<jats:sub>NM<\/jats:sub> from <jats:italic>Neisseria meningitides<\/jats:italic> and ASBT<jats:sub>Yf<\/jats:sub> from <jats:italic>Yersinia frederiksenii<\/jats:italic>) in different conformations. However, one important issue is that the only outward-facing structure (PDB entry 4n7x) was obtained with an Na<jats:sup>+<\/jats:sup>-binding site mutant of ASBT<jats:sub>Yf<\/jats:sub>, which severely cripples its transport function, and therefore the physiological relevance of the conformation in PDB entry 4n7x requires further careful evaluation. Here, another crystal structure is reported of ASBT<jats:sub>Yf<\/jats:sub> that was captured in a state closely resembling the conformation in PDB entry 4n7x using an engineered disulfide bridge. The introduced cysteine mutations avoided any proposed Na<jats:sup>+<\/jats:sup>- or substrate-binding residues, and the resulting mutant retained both structural and functional integrity and behaved similarly to wild-type ASBT<jats:sub>Yf<\/jats:sub>. These data support the hypothesis that the PDB entry 4n7x-like structure represents a functional outward-facing conformation of ASBT<jats:sub>Yf<\/jats:sub> in its transport cycle.<\/jats:p>","DOI":"10.1107\/s205979832001517x","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T14:51:46Z","timestamp":1608303106000},"page":"108-116","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":4,"title":["An engineered disulfide bridge traps and validates an outward-facing conformation in a bile acid transporter"],"prefix":"10.1107","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8917-5805","authenticated-orcid":true,"given":"Xiaodong","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2241-9625","authenticated-orcid":true,"given":"Ying","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8534-2031","authenticated-orcid":true,"given":"Yujia","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3345-1065","authenticated-orcid":true,"given":"Ziyi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8866-7245","authenticated-orcid":true,"given":"Xiaoming","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"329","published-online":{"date-parts":[[2021,1,1]]},"reference":[{"key":"dw5214_bb1","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1107\/S0907444912001308","volume":"68","author":"Afonine","year":"2012","journal-title":"Acta Cryst. 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