ROLE OF LIPID POLYMORPHISM IN G-PROTEIN-MEMBRANE INTERACTIONS - NONLAMELLAR-PRONE PHOSPHOLIPIDS AND PERIPHERAL PROTEIN-BINDING TO MEMBRANES

Heterotrimeric G proteins (peripheral proteins) conduct signals from m embrane receptors (integral proteins) to regulatory proteins localized to various cellular compartments, They are in excess over any G prote in-coupled receptor type on the cell membrane, which is necessary for signal amplification. These facts account for the large number of G pr otein molecules bound to membrane lipids, Thus, the protein-lipid inte ractions are crucial for their cellular localization, and consequently for signal transduction, In this work, the binding of G protein subun its to model membranes (liposomes), formed with defined membrane lipid s, has been studied, It is shown that although G protein alpha-subunit s were able to bind to lipid bilayers, the presence of nonlamellarpron e phospholipids (phosphatidylethanolamines) enhanced their binding to model membranes, This mechanism also appears to be used by other (stru cturally and functionally unrelated) peripheral proteins, such as prot ein kinase C and the insect protein apolipophorin III, indicating that it could constitute a general mode of protein-lipid interactions, rel evant in the activity and translocation of some peripheral (amphitropi c) proteins from soluble to particulate compartments, Other factors, s uch as the presence of cholesterol or the vesicle surface charge, also modulated the binding of the G protein subunits to lipid bilayers, Co nversely, the binding of G protein-coupled receptor kinase 2 and the G protein beta-subunit to liposomes was not increased by hexagonally pr one lipids, Their distinct interactions with membrane lipids may, in p art, explain the different cellular localizations of all of these prot eins during the signaling process.