Tripartite Assembly of RND Multidrug Efflux Pumps

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Feb 13

PMID 26867482

Citations 77

Authors

Laetitia Daury

Francois Orange

Jean-Christophe Taveau

Alice Verchere

Laura Monlezun

Celine Gounou

Ravi K R Marreddy

Martin Picard

Isabelle Broutin

Klaas M Pos

Olivier Lambert

Affiliations

Soon will be listed here.

Abstract

Tripartite multidrug efflux systems of Gram-negative bacteria are composed of an inner membrane transporter, an outer membrane channel and a periplasmic adaptor protein. They are assumed to form ducts inside the periplasm facilitating drug exit across the outer membrane. Here we present the reconstitution of native Pseudomonas aeruginosa MexAB-OprM and Escherichia coli AcrAB-TolC tripartite Resistance Nodulation and cell Division (RND) efflux systems in a lipid nanodisc system. Single-particle analysis by electron microscopy reveals the inner and outer membrane protein components linked together via the periplasmic adaptor protein. This intrinsic ability of the native components to self-assemble also leads to the formation of a stable interspecies AcrA-MexB-TolC complex suggesting a common mechanism of tripartite assembly. Projection structures of all three complexes emphasize the role of the periplasmic adaptor protein as part of the exit duct with no physical interaction between the inner and outer membrane components.

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