Lipid bilayer composition influences small multidrug transporters.
BACKGROUND
Membrane proteins are influenced by their surrounding lipids. We investigate the effect of bilayer composition on the membrane transport activity of two members of the small multidrug resistance family; the Escherichia coli transporter, EmrE and the Mycobacterium tuberculosis, TBsmr. In particular we address the influence of phosphatidylethanolamine and anionic lipids on the activity of these multidrug transporters. Phosphatidylethanolamine lipids are native to the membranes of both transporters and also alter the lateral pressure profile of a lipid bilayer. Lipid bilayer lateral pressures affect membrane protein insertion, folding and activity and have been shown to influence reconstitution, topology and activity of membrane transport proteins.


RESULTS
Both EmrE and TBsmr are found to exhibit a similar dependence on lipid composition, with phosphatidylethanolamine increasing methyl viologen transport. Anionic lipids also increase transport for both EmrE and TBsmr, with the proteins showing a preference for their most prevalent native anionic lipid headgroup; phosphatidylglycerol for EmrE and phosphatidylinositol for TBsmr.


CONCLUSIONS
These findings show that the physical state of the membrane modifies drug transport and that substrate translocation is dependent on in vitro lipid composition. Multidrug transport activity seems to respond to alterations in the lateral forces exerted upon the transport proteins by the bilayer.
Charalambous
Kalypso
K
Department of Biochemistry, University of Bristol, Bristol BS8 1TD, UK. k.charalambous@mail.cryst.bbk.ac.uk
Miller
David
D
Curnow
Paul
P
Booth
Paula J
PJ
D017920:Antiporters / Q000378:metabolism*; D001692:Biological Transport; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D008745:Methylation; D014755:Viologens / Q000737:chemistry / Q000378:metabolism
D017920:Antiporters; D029968:Escherichia coli Proteins; D008051:Lipid Bilayers; D014755:Viologens; C075436:EmrE protein, E coli