Natural Sciences and Engineering Research Council (NSERC, Canada)
RGPIN-2016-04898
カナダ
Natural Sciences and Engineering Research Council (NSERC, Canada)
RGPIN-2014-04798
カナダ
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI052293
米国
Canadian Institutes of Health Research (CIHR)
MOP 86693
カナダ
Other private
University of Melbourne- Start-up Funds
オーストラリア
引用
ジャーナル: Structure / 年: 2021 タイトル: A "Drug Sweeping" State of the TriABC Triclosan Efflux Pump from Pseudomonas aeruginosa. 著者: Lucien Fabre / Abigail T Ntreh / Amira Yazidi / Inga V Leus / Jon W Weeks / Sudipta Bhattacharyya / Jakob Ruickoldt / Isabelle Rouiller / Helen I Zgurskaya / Jurgen Sygusch / 要旨: The structure of the TriABC inner membrane component of the triclosan/SDS-specific efflux pump from Pseudomonas aeruginosa was determined by cryoelectron microscopy to 4.5 Å resolution. The ...The structure of the TriABC inner membrane component of the triclosan/SDS-specific efflux pump from Pseudomonas aeruginosa was determined by cryoelectron microscopy to 4.5 Å resolution. The complete structure of the inner membrane transporter TriC of the resistance-nodulation-division (RND) superfamily was solved, including a partial structure of the fused periplasmic membrane fusion subunits, TriA and TriB. The substrate-free conformation of TriABC represents an intermediate step in efflux complex assembly before the engagement of the outer membrane channel. Structural analysis identified a tunnel network whose constriction impedes substrate efflux, indicating inhibition of TriABC in the unengaged state. Blind docking studies revealed binding to TriC at the same loci by substrates and bulkier non-substrates. Together with functional analyses, we propose that selective substrate translocation involves conformational gating at the tunnel narrowing that, together with conformational ordering of TriA and TriB, creates an engaged state capable of mediating substrate efflux.
EMPIAR-10128 (タイトル: A "drug sweeping" state of the TriABC triclosan efflux pump from Pseudomonas aeruginosa Data size: 238.7 Data #1: Unaligned multi-frame micrographs [micrographs - multiframe] Data #2: Single particles stacks with polished particles [picked particles - multiframe - processed] Data #3: Relion repertory of the final refinement with a symmetry C3 [picked particles - single frame - processed] Data #4: Relion repertory of the final refinement with no symmetry [picked particles - multiframe - processed])