Role of hydrophobic forces in membrane protein asymmetry

Abstract

M13 virus coat protein is an integral cytoplasmic membrane protein at all stages of viral infection. The pure virus coat protein can also be incorporated into synthetic lecithin vesicles near the lipid-phase transition temperature (Tm), spanning the bilayer with its N terminus exposed on the outside and its C-terminus inside (Wickner, W. (1976), Proc. Natl. Acad. Sci. U.S.A. 73, 1159-1163). The assembly of coat protein into vesicles in this asymmetric fashion has a sharp maximum near the phase-transition temperature of the lipid fatty acyl chains. At temperatures well below the Tm, coat protein assembles into lecithin vesicles with both termini exposed on the exterior vesicle surface. In contrast to this important role of lipid physical state, asymmetry of assembly is unaffected by parameters which govern polar interactions such as pH, ionic strength, lipid polar head group, or prior proteolytic removal of either the N or C terminus. It is proposed that the orientation of this membrane protein, and perhaps others, is determined by interactions of the hydrophobic portion of the protein with the lipid hydrocarbon core.