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A role for the periplasmic adaptor protein AcrA in vetting substrate access to the RND efflux transporter AcrB

Alav, Ilyas and Bavro, Vassiliy N and Blair, Jessica MA (2022) 'A role for the periplasmic adaptor protein AcrA in vetting substrate access to the RND efflux transporter AcrB.' Scientific Reports, 12 (1). 4752-. ISSN 2045-2322

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Abstract

Tripartite resistance-nodulation-division (RND) efflux pumps, such as AcrAB-TolC of Salmonella Typhimurium, contribute to antibiotic resistance and comprise an inner membrane RND-transporter, an outer membrane factor, and a periplasmic adaptor protein (PAP). The role of the PAP in the assembly and active transport process remains poorly understood. Here, we identify the functionally critical residues involved in PAP-RND-transporter binding between AcrA and AcrB and show that the corresponding RND-binding residues in the closely related PAP AcrE, are also important for its interaction with AcrB. We also report a residue in the membrane-proximal domain of AcrA, that when mutated, differentially affects the transport of substrates utilising different AcrB efflux channels, namely channels 1 and 2. This supports a potential role for the PAP in sensing the substrate-occupied state of the proximal binding pocket of the transporter and substrate vetting. Understanding the PAP’s role in the assembly and function of tripartite RND pumps can guide novel ways to inhibit their function to combat antibiotic resistance.

Item Type: Article
Uncontrolled Keywords: Periplasm; Salmonella typhimurium; Adaptor Proteins, Signal Transducing; Bacterial Outer Membrane Proteins; Escherichia coli Proteins; Membrane Transport Proteins; Multidrug Resistance-Associated Proteins; Anti-Bacterial Agents; Biological Transport
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 21 Mar 2022 15:11
Last Modified: 02 May 2022 13:00
URI: http://repository.essex.ac.uk/id/eprint/32573

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