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

Hyeongseop Jeong, Jin Sik Kim, Saemee Song, Hideki Shigematsu, Takeshi Yokoyama, Jaekyung Hyun, Nam Chul Ha

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)272-276
Number of pages5
JournalStructure
Volume24
Issue number2
DOIs
Publication statusPublished - 2016 Feb 2
Externally publishedYes

Keywords

  • Complex structure
  • Cryo-electron microscopy
  • Membrane protein
  • Multidrug efflux pump

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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