Pseudoatomic Structure of the Tripartite Multidrug Efflux Pump AcrAB-TolC Reveals the Intermeshing Cogwheel-like Interaction between AcrA and TolC

Structure
Hyeongseop JeongNam-Chul Ha

Abstract

The resistance-nodulation-division type tripartite pump AcrAB-TolC and its homologs are responsible for multidrug resistance in Gram-negative bacteria by expelling a wide variety of toxic substrates. The three essential components, AcrA, AcrB, and TolC, must function in concert with each respective binding partner within the complex. In this study, we report an 8.2-Å resolution cryo-electron microscopy (cryo-EM) 3D reconstruction of the complex that consists of an AcrAB fusion protein and a chimeric TolC protein. The pseudoatomic structure derived from the cryo-EM reconstruction clearly demonstrates a model only compatible with the adaptor bridging mechanism, wherein the funnel-like AcrA hexamer forms an intermeshing cogwheel-like interaction with the α-barrel tip region of TolC. These observations provide a structural milestone for understanding multidrug resistance in pathogenic Gram-negative bacteria, and may also lead to the design of new antibacterial drugs.

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Citations

May 16, 2017·Nature Microbiology·Anthony W P FitzpatrickDijun Du
Dec 1, 2017·Scientific Reports·Cesar A LópezS Gnanakaran
Dec 15, 2017·Biophysical Reports·Xuejun C ZhangLei Han
Apr 21, 2019·Medicinal Research Reviews·Andraž LamutTihomir Tomašič
Sep 11, 2020·International Journal of Microbiology·Sergio D Rodríguez-CamarilloFernando Martínez-Ocampo
Mar 15, 2019·Scientific Reports·Keisuke SakuraiRyosuke Nakashima
Oct 8, 2019·Annals of the New York Academy of Sciences·Jessica KobylkaKlaas M Pos
Feb 20, 2019·Nature Communications·Christopher A CaffaletteJochen Zimmer
Jan 30, 2019·Biophysical Journal·Zbigniew M DarzynkiewiczHelen I Zgurskaya
Sep 14, 2019·ACS Infectious Diseases·Anthony J HazelJames C Gumbart

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