New Developments in Lipid-Protein Interactions and Receptor Function

Abstract

Analogous to the dependence of soluble enzymes on the composition and characteristics of their aqueous milieu, the activity of functional membrane proteins is influenced by properties of the lipid bilayer. Specifically, in numerous studies the function of membrane-bound enzymes, receptors and transport carriers was correlated with membrane fluidity, a biophysical property largely determined by membrane composition at a given temperature (Shinitzky, 1987a; Aloia et al., 1988; Viret et al., 1990). The results of these studies have confirmed the significance of membrane microviscosity as a parameter that affects the dynamics and thereby, the biological activity of various membrane constituents. As shown in progressively fluidized membrane of turkey erythrocytes, the activation of adenylate cyclase following occupancy of the ß-adrenergic receptor is a diffusion-controlled process (Hanski et al., 1978). This model depicts the receptor and enzyme as mobile membrane components whose diffusion leads to collision-coupling and initiates signal generation. Thus, in this system, the fluidity of the membrane microenvironment has at least a modulating, if not a ratelimiting role. In contrast, in permanently coupled systems, such as the adenosine receptor, altered membrane microviscosity did not influence the coupling process (Braun and Levitzki, 1979). Both of these modes of coupling can be part of the overall mechanism of a receptor: approximately one-half of the α2-adrenergic receptors that bound to GTP regulatory protein did so by collision-coupling, the others were precoupled (Neubig et al., 1988).