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

TY - JOUR

T1 - Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump

AU - Fitzpatrick, Anthony W. P.

AU - Llabres, Salome

AU - Neuberger, Arthur

AU - Blaza, James N.

AU - Bai, Xiao-Chen

AU - Okada, Ui

AU - Murakami, Satoshi

AU - van Veen, Hendrik W.

AU - Zachariae, Ulrich

AU - Scheres, Sjors H. W.

AU - Luisi, Ben F.

AU - Du, Dijun

N1 - This work was supported by the Wellcome Trust (B.F.L.), HFSP (B.F.L., H.W.v.V., S. M.), Marie Curie International Outgoing Fellowship (A.W.P.F.), the UK Medical Research Council (MC_UP_A025_1013, to SHWS), Wellcome Trust ISSF award (grant number: WT097818MF), the Scottish Universities’ Physics Alliance (U.Z. and S.L.) and MRC Mitochondrial Biology Unit (Grant number: U105663141). A.N. is the recipient of a Herchel-Smith Scholarship.

PY - 2017/5/15

Y1 - 2017/5/15

N2 - 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.

AB - 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.

KW - ABC transporter

KW - drug efflux pump

KW - multi-drug resistance

KW - macrolide transporter

KW - toxin transporter

U2 - 10.1038/nmicrobiol.2017.70

DO - 10.1038/nmicrobiol.2017.70

M3 - Article

C2 - 28504659

SN - 2058-5276

VL - 2

SP - 1

EP - 8

JO - Nature Microbiology

JF - Nature Microbiology

M1 - 17070

ER -