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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-6238

Seeger, M A; von Ballmoos, C; Eicher, T; Brandstätter, L; Verrey, F; Diederichs, K; Pos, K M (2008). Engineered disulfide bonds support the functional rotation mechanism of multidrug efflux pump AcrB. Nature Structural and Molecular Biology, 15(2):199-205.

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Abstract

The AcrA-AcrB-TolC complex is the major multidrug efflux pump in Escherichia coli. The asymmetric structure of the trimeric inner-membrane component AcrB implies functional rotation of the monomers and a peristaltic mode of drug efflux. This mechanism suggests the occurrence of conformational changes in the periplasmic pore domain through the movements of subdomains during cycling of the monomers through the different states loose (L), tight (T) and open (O). We introduced cysteines at the interfaces of potentially moving subdomains, leading to disulfide bond formation as quantified by alkylation of free cysteines and MALDI-TOF analysis. Inhibition of pump function as a result of cross-linking caused increased susceptibility to noxious compounds and reduction of N-phenylnaphthylamine efflux. Regain of function for impaired mutants was obtained upon exposure to the reducing agent DTT. The results support the presence of the asymmetric AcrB trimer in E. coli membranes and the functional rotation mechanism.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:10 Dec 2008 09:30
Last Modified:27 Nov 2013 19:34
Publisher:Nature Publishing Group
ISSN:1545-9985
Publisher DOI:10.1038/nsmb.1379
PubMed ID:18223659
Citations:Web of Science®. Times Cited: 66
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Scopus®. Citation Count: 70

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