To determine how the lipid environment affects membrane protein structure and function, strains of Escherichia coli were developed in which normal phospholipid composition can be altered or foreign lipids can be introduced. The properties of LacY (lactose permease) were investigated as a function of lipid environment. Assembly of LacY in membranes lacking PE (phosphatidylethanolamine) results in misorientation of the N-terminal six-TM (transmembrane domain) helical bundle with loss of energy-dependent uphill transport and retention of energy-independent downhill transport. Post-assembly introduction of PE results in nearly native orientation of TMs and restoration of uphill transport. Foreign lipids with no net charge can substitute for PE in supporting native LacY topology, but restoration of uphill transport is dependent on native topology and the proper folding of a solvent-exposed domain. Increasing the positive charge density of the cytoplasmically exposed surface of LacY counters TM misorientation in the absence of neutral lipids, demonstrating that charge interactions between these domains and the surface of the membrane bilayer are determinants of TM orientation. Therefore membrane protein organization or reorganization is determined either during initial assembly or post-insertionally through direct interactions between the protein and the lipid environment, which affects the topogenic potency of opposing charged residues as topological signals independent of the translocon.
Skip Nav Destination
Article navigation
June 2011
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
May 20 2011
Lipid–protein interactions as determinants of membrane protein structure and function
William Dowhan;
William Dowhan
1
1Department of Biochemistry and Molecular Biology, University of Texas Medical School-Houston, 6431 Fannin Street, Houston, TX 77030, U.S.A.
1To whom correspondence should be addressed (email William.Dowhan@uth.tmc.edu).
Search for other works by this author on:
Mikhail Bogdanov
Mikhail Bogdanov
1Department of Biochemistry and Molecular Biology, University of Texas Medical School-Houston, 6431 Fannin Street, Houston, TX 77030, U.S.A.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
January 18 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem Soc Trans (2011) 39 (3): 767–774.
Article history
Received:
January 18 2011
Citation
William Dowhan, Mikhail Bogdanov; Lipid–protein interactions as determinants of membrane protein structure and function. Biochem Soc Trans 1 June 2011; 39 (3): 767–774. doi: https://doi.org/10.1042/BST0390767
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.