By the same authors

From the same journal

Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump

Research output: Contribution to journalArticle

Author(s)

  • Anthony W P Fitzpatrick
  • Salomé Llabrés
  • Arthur Neuberger
  • James N Blaza
  • Xiao-Chen Bai
  • Ui Okada
  • Satoshi Murakami
  • Hendrik W van Veen
  • Ulrich Zachariae
  • Sjors H W Scheres
  • Ben F Luisi
  • Dijun Du

Department/unit(s)

Publication details

JournalNature Microbiology
DateAccepted/In press - 3 Apr 2017
DatePublished (current) - 15 May 2017
Volume2
Original languageEnglish

Abstract

The MacA-MacB-TolC assembly of Escherichia coli is a transmembrane machine that spans the cell envelope and actively extrudes substrates, including macrolide antibiotics and polypeptide virulence factors. These transport processes are energized by the ATPase MacB, a member of the ATP-binding cassette (ABC) superfamily. We present an electron cryo-microscopy structure of the ABC-type tripartite assembly at near-atomic resolution. A hexamer of the periplasmic protein MacA bridges between a TolC trimer in the outer membrane and a MacB dimer in the inner membrane, generating a quaternary structure with a central channel for substrate translocation. A gating ring found in MacA is proposed to act as a one-way valve in substrate transport. The MacB structure features an atypical transmembrane domain with a closely packed dimer interface and a periplasmic opening that is the likely portal for substrate entry from the periplasm, with subsequent displacement through an allosteric transport mechanism.

    Research areas

  • ATP-Binding Cassette Transporters/chemistry, Bacterial Outer Membrane Proteins/chemistry, Cryoelectron Microscopy, Escherichia coli/chemistry, Escherichia coli Proteins/chemistry, Membrane Transport Proteins/chemistry, Models, Molecular, Protein Conformation, Protein Multimerization

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