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Although several substrate-entrances have been identified, the specificity of these various transport paths remains unclear. Here we present evidence for a substrate channel (channel 3) \u00a0from the central cavity of the AcrB trimer, which is connected directly to the\u00a0deep pocket without first passing the switch-loop and the proximal pocket . Planar aromatic cations, such as ethidium, prefer channel 3 to channels 1 and 2. The efflux through channel 3 increases by targeted mutations and is not in competition with the export of drugs such as minocycline and erythromycin through channels 1 and 2. A switch-loop mutant, in which the pathway from the proximal to the deep pocket is hindered, can export only channel 3-utilizing drugs. The usage of multiple entrances thus contributes to the recognition and transport of a wide range of drugs with different physicochemical properties.\n                  <\/jats:p>","DOI":"10.1038\/s41467-017-02493-1","type":"journal-article","created":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T12:34:01Z","timestamp":1514982841000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Multiple entry pathways within the efflux transporter AcrB contribute to multidrug recognition"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9081-382X","authenticated-orcid":false,"given":"Martijn","family":"Zwama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Yamasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6948-1899","authenticated-orcid":false,"given":"Keisuke","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3349-1769","authenticated-orcid":false,"given":"Kunihiko","family":"Nishino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8083-7609","authenticated-orcid":false,"given":"Akihito","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,9]]},"reference":[{"key":"2493_CR1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/nrmicro1464","volume":"4","author":"LJV Piddock","year":"2006","unstructured":"Piddock, L. 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