Recombinant Escherichia coli Multidrug efflux pump subunit AcrA (acrA)

Function

Periplasmic adaptor component of the AcrAB-TolC efflux system that confers multidrug resistance (PubMed:9878415). The AcrAB-TolC efflux system has a broad substrate specificity, acting as a substrate:proton antiporter, using proton motive force to export substrates (Probable). AcrA is elongated in shape, being long enough to span the periplasm, linking AcrB and TolC stably together, perhaps promoted by binding to peptidoglycan (PubMed:22308040, PubMed:9878415). AcrA is also a component of the AcrABZ-TolC efflux system, where the small accessory protein AcrZ, together with membrane lipids, may influence the specificity of drug export (PubMed:23010927, PubMed:28355133)

Subcellular Location

Cell inner membrane (Lipid-anchor)

Subunit

Monomeric in solution (PubMed:9878415). Homotrimeric (PubMed:16079137). Component of the AcrAB-TolC multidrug efflux complex, composed of six AcrA subunits forming a hexameric tube, binding to a AcrB trimer, which interact with the trimeric TolC outer membrane channel protein (PubMed:10920254, PubMed:15228545, PubMed:28355133, PubMed:31201302). Complex assembly may be independent of an efflux substrate and appears to be constitutive; AcrA may adopt two conformationally distinct protomers in the assembled pump (PubMed:15228545, PubMed:28355133). TolC is thought to not directly contact AcrB; instead, AcrA joins AcrB and TolC by forming a funnel-like hexamer anchored to the inner membrane (PubMed:15228545, PubMed:28355133, PubMed:31201302). AcrA may initially form a hexameric ring complex with AcrB, in a bipartite complex, which may be stabilized by binding of AcrA with the peptidoglycan layer, prior to forming the full AcrAB-TolC efflux pump complex (PubMed:22308040, PubMed:28355133, PubMed:31201302). Contact between AcrA-AcrB and TolC may prompt a conformational change in the presence of substrate, allowing the periplasmic gate to open (PubMed:28355133, PubMed:31201302). It is thought that, under high intracellular substrate concentration, AcrB ejects substrate into the tunnel formed by AcrA-TolC; as the substrate level declines, conformational changes in AcrB cause efflux to reduce and stop and the complex shifts to the closed state (PubMed:31201302). Component of the AcrABZ-TolC efflux pump complex, composed of six AcrA subunits forming a hexameric tube binding to an AcrB trimer, which interact with the trimeric TolC outer membrane channel protein; AcrZ interacts directly with AcrB, probably in 1:1 stoichiometry (PubMed:23010927, PubMed:28355133)

• Ma D. et al. Molecular cloning and characterization of acrA and acrE genes of Escherichia coli. — J. Bacteriol. (1993)
• Xu J. et al. Nucleotide sequence of the acrAB operon from Escherichia coli. (MAY-)
• Chung E. et al. Sequence of minutes 4-25 of Escherichia coli. (JAN-)
• Blattner F.R. et al. The complete genome sequence of Escherichia coli K-12. — Science (1997)
• Hayashi K. et al. Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. — Mol. Syst. Biol. (2006)
• Ma D. et al. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. — Mol. Microbiol. (1995)
• Zgurskaya H.I. et al. AcrA is a highly asymmetric protein capable of spanning the periplasm. — J. Mol. Biol. (1999)
• Kawabe T. et al. Molecular construction of a multidrug exporter system, AcrAB: molecular interaction between AcrA and AcrB, and cleavage of the N-terminal signal sequence of AcrA. — J. Biochem. (2000)