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

Adaptor Proteins, Signal Transducing / metabolism Anti-Bacterial Agents / metabolism Bacterial Outer Membrane Proteins / metabolism Biological Transport Escherichia coli Proteins / genetics Membrane Transport Proteins / genetics Multidrug Resistance-Associated Proteins / genetics Periplasm / metabolism Salmonella typhimurium / genetics

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
19 03 2022
Historique:
received: 19 10 2021
accepted: 14 03 2022
entrez: 20 3 2022
pubmed: 21 3 2022
medline: 20 4 2022
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41598-022-08903-9 PMID: 35306531 PMC: PMC8934357
pubmed: 35306531
doi: 10.1038/s41598-022-08903-9
pii: 10.1038/s41598-022-08903-9
pmc: PMC8934357
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Anti-Bacterial Agents 0
Bacterial Outer Membrane Proteins 0
Escherichia coli Proteins 0
Membrane Transport Proteins 0
Multidrug Resistance-Associated Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4752

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M01116X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N002776/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M02623X/1
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Ilyas Alav (I)

Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.

Vassiliy N Bavro (VN)

School of Life Sciences, University of Essex, Colchester, CO4 3SQ, UK. v.bavro@essex.ac.uk.

Jessica M A Blair (JMA)

Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK. j.m.a.blair@bham.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › A role for the periplasmic adaptor protein...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antibactériens › A role for the periplasmic adaptor protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de la membrane externe bactérienne › A role for the periplasmic adaptor protein...
questionsmedicales.fr › Métabolisme › Transport biologique › A role for the periplasmic adaptor protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines bactériennes › Protéines Escherichia coli › A role for the periplasmic adaptor protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › A role for the periplasmic adaptor protein...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Transporteurs d'anions organiques ATP-dépendants › Protéines associées à la multirésistance aux médicaments › A role for the periplasmic adaptor protein...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace extracellulaire › Périplasme › A role for the periplasmic adaptor protein...
questionsmedicales.fr › Bactéries › Proteobacteria › Gammaproteobacteria › Enterobacteriaceae › Salmonella › Salmonella enterica › Salmonella typhimurium › A role for the periplasmic adaptor protein...