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Adv."],"published-print":{"date-parts":[[2026,8,7]]},"abstract":"<jats:p>\n                    Resistance\u2013nodulation\u2013cell division (RND) efflux pumps are the major cause of multidrug resistance in\n                    <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                    . The inner membrane protein MexK from\n                    <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    is a narrow-spectrum RND transporter. It assembles with membrane fusion protein MexJ and outer membrane proteins to form a tripartite efflux complex that efficiently exports drugs like triclosan. Here, we resolve the cryo-EM structures of apo-MexK at 3.4-angstrom resolution and the triclosan-bound MexJK complex at 2.6-angstrom resolution. Besides the unique architectural features of MexK, our structural data reveal a triclosan-binding pocket within the transmembrane domain of MexK protomers, distinct from known substrate-binding sites in other RND transporters. Using molecular dynamics simulations and mutagenesis, we elucidate a previously uncharacterized triclosan transport tunnel across the inner membrane with cytosolic access. The key residues for triclosan efflux are further shown essential for two other potential substrates of MexK, chloramphenicol and pyrimethamine. Our results provide the molecular basis for an unusual drug trafficking pathway in RND efflux pumps.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee7036","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:59:18Z","timestamp":1786125558000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Structural insights into a substrate translocation pathway revealed by the RND efflux pump complex MexJK from\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1957-3540","authenticated-orcid":true,"given":"Zhikun","family":"Wu","sequence":"first","affiliation":[{"name":"Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, 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