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TitleA "Drug Sweeping" State of the TriABC Triclosan Efflux Pump from Pseudomonas aeruginosa.
Journal, issue, pagesStructure, Vol. 29, Issue 3, Page 261-274.e6, Year 2021
Publish dateMar 4, 2021
AuthorsLucien Fabre / Abigail T Ntreh / Amira Yazidi / Inga V Leus / Jon W Weeks / Sudipta Bhattacharyya / Jakob Ruickoldt / Isabelle Rouiller / Helen I Zgurskaya / Jurgen Sygusch /
PubMed AbstractThe 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.
External linksStructure / PubMed:32966762 / PubMed Central
MethodsEM (single particle)
Resolution4.3 - 20.0 Å
Structure data

EMDB-21361:
TriABC triclosan efflux pump from Pseudomonas aeruginosa- No symmetry
Method: EM (single particle) / Resolution: 6.5 Å

EMDB-21362:
Negative stain map of TriABC triclosan efflux pump from Pseudomonas aeruginosa
Method: EM (single particle) / Resolution: 20.0 Å

EMDB-21363: Cryo-EM map of TriABC triclosan efflux pump from Pseudomonas aeruginosa
PDB-6vej: TriABC transporter from Pseudomonas aeruginosa
Method: EM (single particle) / Resolution: 4.3 Å

Chemicals

ChemComp-LMU:
DODECYL-ALPHA-D-MALTOSIDE / detergent*YM

ChemComp-E2V:
(2R)-2-(hexadecanoyloxy)propyl nonadecanoate

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

Source
  • pseudomonas aeruginosa (bacteria)
KeywordsTRANSPORT PROTEIN / RND transporter / Pseudomonas aeruginosa / transmembrane / TriABC / TriC / PMF / cryoEM

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