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

DOI: 10.1038/nmicrobiol.2017.70

Authors: Anthony Fitzpatrick (University of Cambridge) , Salomé Llabrés (University of Dundee) , Arthur Neuberger (University of Cambridge) , James N. Blaza (MRC Mitochondrial Biology Unit, University of Cambridge) , Xiao-Chen Bai (MRC Mitochondrial Biology Unit, University of Cambridge) , Ui Okada (Tokyo Institute of Technology) , Satoshi Murakami (Tokyo Institute of Technology) , Hendrik W. Van Veen (University of Cambridge) , Ulrich Zachariae (University of Dundee) , Sjors H. W. Scheres (University of Cambridge) , Ben F. Luisi (University of Cambridge) , Dijun Du (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Microbiology , VOL 2

State: Published (Approved)
Published: May 2017

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.

Journal Keywords: Antimicrobial resistance; Bacterial structural biology; Cryoelectron microscopy; Transporters

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Added On: 23/11/2017 14:40

Discipline Tags:

Pathogens Antibiotic Resistance Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)