Structure of the MacAB–TolC ABC-type tripartite multidrug efflux pump
Published in Nature Microbiology, 2017
Recommended citation: Fitzpatrick AWP., Llabrés S., Neuberger A., Blaza JN., Bai X., Okada U., Murakami S., van Veen HW, Zachariae U., Scheres S.H.W., Luisi B.F. Du D. (2017) Nature Microbiology. 2, 17070. hhttps://www.nature.com/articles/nmicrobiol201770
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.
Recommended citation: Fitzpatrick AWP., Llabrés S., Neuberger A., Blaza JN., Bai X., Okada U., Murakami S., van Veen HW, Zachariae U., Scheres S.H.W., Luisi B.F. Du D. (2017) Nature Microbiology. 2, 17070.