Journal
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
Volume 79, Issue 10, Pages 2936-2945Publisher
WILEY-BLACKWELL
DOI: 10.1002/prot.23143
Keywords
allostery; membrane protein; transporter; cross correlation; docking
Categories
Funding
- National High Technology Research Program of China [2006AA02A320]
- National Major Basic Research Program of China [200903918600, 2011CB808505]
- National Science Foundation of China [20973040, 31070642]
- Science & Technology Commission of Shanghai Municipality [08DZ2270500]
- Shanghai Leading Academic Discipline Project [B108]
Ask authors/readers for more resources
The AcrAB-TolC drug efflux system, energized by proton movement down the transmembrane electrochemical gradient, is responsible for the resistance of the organism to a wide range of drugs. Experimental data suggest functional roles of each part of the assembly, but the detailed working mechanism of this machinery remains elusive. We used elastic network-based normal mode analysis (NMA) to explore the conformational dynamics of the AcrAB-TolC complex. The intrinsic flexibilities of the pore domain in AcrB monomer conform to the previously proposed three-step functionally rotating mechanism for asymmetric AcrB trimer. Conformational couplings across monomers in the AcrB trimer were observed, and the coupling between the transmembrane domain and the other parts of AcrB are strengthened through trimeric assembly. In the tripartite AcrAB-TolC assembly obtained through molecular docking, concerted motions were observed not only at the direct contact interfaces between various components but also between distant parts of the whole complex. The presence of AcrA was shown to significantly strengthen the motional couplings between AcrB and TolC. Overall, NMA revealed an allosteric network in the AcAB-TolC efflux system, which provides hints to our understanding of its detailed working mechanism.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available