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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish (US)
Article number17070
JournalNature Microbiology
Volume2
DOIs
StatePublished - May 15 2017

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Lepidium
Adenosine Triphosphate
Periplasmic Proteins
Cryoelectron Microscopy
Periplasm
Membranes
Macrolides
Virulence Factors
Adenosine Triphosphatases
Escherichia coli
Anti-Bacterial Agents
Peptides

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

Cite this

Fitzpatrick, A. W. P., Llabrés, S., Neuberger, A., Blaza, J. N., Bai, X. C., Okada, U., ... Du, D. (2017). Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump. Nature Microbiology, 2, [17070]. https://doi.org/10.1038/nmicrobiol.2017.70

Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump. / Fitzpatrick, Anthony W.P.; Llabrés, Salomé; Neuberger, Arthur; Blaza, James N.; Bai, Xiao Chen; Okada, Ui; Murakami, Satoshi; Van Veen, Hendrik W.; Zachariae, Ulrich; Scheres, Sjors H.W.; Luisi, Ben F.; Du, Dijun.

In: Nature Microbiology, Vol. 2, 17070, 15.05.2017.

Research output: Contribution to journalArticle

Fitzpatrick, AWP, Llabrés, S, Neuberger, A, Blaza, JN, Bai, XC, Okada, U, Murakami, S, Van Veen, HW, Zachariae, U, Scheres, SHW, Luisi, BF & Du, D 2017, 'Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump', Nature Microbiology, vol. 2, 17070. https://doi.org/10.1038/nmicrobiol.2017.70
Fitzpatrick AWP, Llabrés S, Neuberger A, Blaza JN, Bai XC, Okada U et al. Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump. Nature Microbiology. 2017 May 15;2. 17070. https://doi.org/10.1038/nmicrobiol.2017.70
Fitzpatrick, Anthony W.P. ; Llabrés, Salomé ; Neuberger, Arthur ; Blaza, James N. ; Bai, Xiao Chen ; Okada, Ui ; Murakami, Satoshi ; Van Veen, Hendrik W. ; Zachariae, Ulrich ; Scheres, Sjors H.W. ; Luisi, Ben F. ; Du, Dijun. / Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump. In: Nature Microbiology. 2017 ; Vol. 2.
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