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 - Llabrés, Salomé

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

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 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 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 - ATP-Binding Cassette Transporters/chemistry

KW - Bacterial Outer Membrane Proteins/chemistry

KW - Cryoelectron Microscopy

KW - Escherichia coli/chemistry

KW - Escherichia coli Proteins/chemistry

KW - Membrane Transport Proteins/chemistry

KW - Models, Molecular

KW - Protein Conformation

KW - Protein Multimerization

U2 - 10.1038/nmicrobiol.2017.70

DO - 10.1038/nmicrobiol.2017.70

M3 - Article

C2 - 28504659

SN - 2058-5276

VL - 2

JO - Nature Microbiology

JF - Nature Microbiology

M1 - 17070

ER -