| On the role of TolC in multidrug efflux: the function and assembly of AcrAB-TolC tolerate significant depletion of intracellular TolC protein. | |
| | |
MedLine Citation:
|
PMID: 23331412 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
TolC channel provides a route for the expelled drugs and toxins to cross the outer membrane of Escherichia coli. The puzzling feature of TolC structure is that the periplasmic entrance of the channel is closed by dense packing of 12 α-helices. Efflux pumps exemplified by AcrAB are proposed to drive the opening of TolC channel. How interactions with AcrAB promote the close-to-open transition in TolC remains unclear. In this study, we investigated in vivo the functional and physical interactions of AcrAB with the closed TolC and its conformer opened by mutations in the periplasmic entrance. We found that the two conformers of TolC are readily distinguishable in vivo by characteristic drug susceptibility, thiol modification and proteolytic profiles. However, these profiles of TolC variants respond neither to the in vivo stoichiometry of AcrAB:TolC nor to the presence of vancomycin, which is used often to assess the permeability of TolC channel. We further found that the activity and assembly of AcrAB-TolC tolerates significant changes in amounts of TolC and that only a small fraction of intracellular TolC is likely used to support efflux needs of E. coli. Our findings explain why TolC is not a good target for inhibition of multidrug efflux. |
| | |
Authors:
|
Ganesh Krishnamoorthy; Elena B Tikhonova; Girija Dhamdhere; Helen I Zgurskaya |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2013-1-21 |
Journal Detail:
|
Title: Molecular microbiology Volume: - ISSN: 1365-2958 ISO Abbreviation: Mol. Microbiol. Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-1-21 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8712028 Medline TA: Mol Microbiol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
© 2013 Blackwell Publishing Ltd. |
Affiliation:
|
Department of Chemistry and Biochemistry, University of Oklahoma, Stephenson Life Science Research Center, Norman, OK, 73019, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Basic competence in intensive and critical care nursing: development and psychometric testing of a c...
Next Document: Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characterist...