NDLI: Repressive mutations restore function-loss caused by the disruption of trimerization in Escherichia coli multidrug transporter AcrB

Content Provider	PubMed Central
Author	Wang, Zhaoshuai Zhong, Meng Lu, Wei Chai, Qian Wei, Yinan
Copyright Year	2015
Abstract	AcrAB-TolC and their homologs are major multidrug efflux systems in Gram-negative bacteria. The inner membrane component AcrB functions as a trimer. Replacement of Pro223 by Gly in AcrB decreases the trimer stability and drastically reduces the drug efflux activity. The goal of this study is to identify suppressor mutations that restore function to mutant AcrBP223G and explore the mechanism of function recovery. Two methods were used to introduce random mutations into the plasmid of AcrBP223G. Mutants with elevated drug efflux activity were identified, purified, and characterized to examine their expression level, trimer stability, interaction with AcrA, and substrate binding. Nine single-site repressor mutations were identified, including T199M, D256N, A209V, G257V, M662I, Q737L, D788K, P800S, and E810K. Except for M662I, all other mutations located in the docking region of the periplasmic domain. While three mutations, T199M, A209V, and D256N, significantly increased the trimer stability, none of them restored the trimer affinity to the wild type level. M662, the only site of mutation that located in the porter domain, was involved in substrate binding. Our results suggest that the function loss resulted from compromised AcrB trimerization could be restored through various mechanisms involving the compensation of trimer stability and substrate binding.
Related Links	http://dx.doi.org/10.3389/fmicb.2015.00004
Starting Page	4
File Format	PDF
ISSN	1664302X
e-ISSN	1664302X
Journal	Frontiers in Microbiology
Volume Number	6
Language	English
Publisher	Frontiers Media S.A.
Publisher Date	2015-01-01
Access Restriction	Open
Rights Holder	Frontiers Media S.A.
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Microbiology Microbiology (medical)

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Repressive mutations restore function-loss caused by the disruption of trimerization in Escherichia coli multidrug transporter AcrB

Vestibules Are Part of the Substrate Path in the Multidrug Efflux Transporter AcrB of Escherichia coli ▿

Substrate-dependent dynamics of the multidrug efflux transporter AcrB of Escherichia coli

Substrate path in the AcrB multidrug efflux pump of Escherichia coli

Random Mutagenesis of the Multidrug Transporter AcrB from Escherichia coli for Identification of Putative Target Residues of Efflux Pump Inhibitors

Some Ligands Enhance the Efflux of Other Ligands by the Escherichia coli Multidrug Pump AcrB

Substrate binding accelerates the conformational transitions and substrate dissociation in multidrug efflux transporter AcrB

Kinetic behavior of the major multidrug efflux pump AcrB of Escherichia coli

Mechanism of recognition of compounds of diverse structures by the multidrug efflux pump AcrB of Escherichia coli

Repressive mutations restore function-loss caused by the disruption of trimerization in Escherichia coli multidrug transporter AcrB

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Repressive mutations restore function-loss caused by the disruption of trimerization in Escherichia coli multidrug transporter AcrB

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Repressive mutations restore function-loss caused by the disruption of trimerization in Escherichia coli multidrug transporter AcrB