Borges-Walmsley, M. I. and Beauchamp, J. and Kelly, S. M. and Jumel, K. and Candlish, D. and Harding, S. E. and Price, N. C. and Walmsley, A. (2003) 'Identification of oligomerization and drug-binding domains of the membrane fusion protein EmrA.', Journal of biological chemistry., 278 (15). pp. 12903-12912.
Many pathogenic Gram-negative bacteria possess tripartite transporters that catalyze drug extrusion across the inner and outer membranes, thereby conferring resistance. These transporters consist of inner (IMP) and outer (OMP) membrane proteins, which are coupled by a periplasmic membrane fusion (MFP) protein. However, it is not know whether the MFP translocates the drug between the membranes, by acting as a channel, or whether it brings the IMP and OMP together, facilitating drug transfer. The MFP EmrA has an elongated periplasmic domain, which binds transported drugs, and is anchored to the inner membrane by a single -helix, which contains a leucine zipper dimerization domain. Consistent with CD and hydrodynamic analyses, the periplasmic domain is predicted to be composed of a -sheet subdomain and an -helical coiled-coil. We propose that EmrA forms a trimer in which the coiled-coils radiate across the periplasm, where they could sequester the OMP TolC. The "free" leucine zipper in the EmrA trimer might stabilize the interaction with the IMP EmrB, which also possesses leucine zipper motifs in the putative N- and C-terminal helices. The -sheet subdomain of EmrA would sit at the membrane surface adjacent to the EmrB, from which it receives the transported drug, inducing a conformational change that triggers the interaction with the OMP.
|Full text:||(VoR) Version of Record|
Download PDF (221Kb)
|Publisher Web site:||https://doi.org/10.1074/jbc.M209457200|
|Publisher statement:||This research was originally published in Journal of Biological Chemistry. Borges-Walmsley, M.I., Beauchamp, J., Kelly, S.M., Jumel, K., Candlish, D., Harding, S.E., Price, N.C. & Walmsley, A. (2003). Identification of oligomerization and drug-binding domains of the membrane fusion protein EmrA. Journal of Biological Chemistry 278(15): 12903-12912. © the American Society for Biochemistry and Molecular Biology.|
|Record Created:||26 Aug 2008|
|Last Modified:||29 Aug 2017 14:53|
|Social bookmarking:||Export: EndNote, Zotero | BibTex|
|Look up in GoogleScholar | Find in a UK Library|