THE EFFECTS OF NON-LAMELLAR FORMING LIPIDS ON MEMBRANE PROTEIN-LIPID INTERACTIONS

The role of lipid polymorphism in the regulation of membrane-associate d protein function is examined, based on recent studies which showed t hat changes in the levels of phosphatidylethanolamine (PE), cholestero l and phospholipid unsaturation, modulate the activity of the key sign al transduction enzyme, protein kinase C (PKC). It is shown that effec ts of membrane compositional changes on PKC activity involve a perturb ation of protein-lipid interactions with the head group region rather than with the hydrophobic interior of the bilayer. A key determinant i n the perturbation of these interactions is suggested to be an elastic curvature energy, termed curvature stress, which results from the unf avorable packing of non-lamellar forming lipids in a planar bilayer. P KC activity is shown to be a biphasic function of curvature stress, wi th an optimum value of this parameter corresponding to an optimally ac tive PKC conformation. Thus, it is shown that the maximal activity of conformationally distinct PKC isoforms may require a different optimum value of curvature stress. Furthermore, it is hypothesized that curva ture stress may have differing effects on the conformation of membrane -associated PKC activity induced by diacylglycerols, phorbol esters or other activators, based on recent studies showing that these agents i nduce the formation of disparate active conformers of the enzyme.