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

Anthony W. P. Fitzpatrick, Salome Llabres, Arthur Neuberger, James N. Blaza, Xiao-Chen Bai, Ui Okada, Satoshi Murakami, Hendrik W. van Veen, Ulrich Zachariae, Sjors H. W. Scheres (Lead / Corresponding author), Ben F. Luisi (Lead / Corresponding author), Dijun Du (Lead / Corresponding author)

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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 (TMD) 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.
Original languageEnglish
Article number17070
Pages (from-to)1-8
Number of pages8
JournalNature Microbiology
Publication statusPublished - 15 May 2017


  • ABC transporter
  • drug efflux pump
  • multi-drug resistance
  • macrolide transporter
  • toxin transporter


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