Modulation of rhodopsin function by properties of the membrane bilayer.
A prevalent model for the function of rhodopsin centers on the metarhodopsin I (MI) to metarhodopsin II (MII) conformational transition as the triggering event for the visual process. Flash photolysis techniques enable one to determine the [MII]/[MI] ratio for rhodopsin in various recombinant membranes, and thus investigate the roles of the phospholipid head groups and the lipid acyl chains systematically. The results obtained to date clearly show that the pK for the acid-base MI-MII equilibrium of rhodopsin is modulated by the lipid environment. In bilayers of phosphatidylcholines the MI-MII equilibrium is shifted to the left; whereas in the native rod outer segment membranes it is shifted to the right, i.e., at neutral pH near physiological temperature. The lipid mixtures sufficient to yield full photochemical function of rhodopsin include a native-like head group composition, viz, comprising phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), in combination with polyunsaturated docosahexaenoic acid (DHA; 22:6 omega 3) chains. Yet such a native-like lipid mixture is not necessary for the MI-MII conformational transition of rhodopsin; one can substitute other lipid compositions having similar properties. The MI-MII transition is favored by relatively small head groups which produce a condensed bilayer surface, viz, a comparatively small interfacial area as in the case of PE, together with bulky acyl chains such as DHA which prefer a relatively large cross sectional area. The resulting force imbalance across the layer gives rise to a curvature elastic stress of the lipid/water interface, such that the lipid mixtures yielding native-like behavior form reverse hexagonal (HII) phases at slightly higher temperatures. A relatively unstable membrane is needed: lipids tending to form the lamellar phase do not support full native-like photochemical function of rhodopsin. Thus chemically specific properties of the various lipids are not required, but rather average or material properties of the entire assembly, which may involve the curvature free energy of the membrane-lipid water interface. These findings reveal that the membrane lipid bilayer has a direct influence on the energetics of the conformational states of rhodopsin in visual excitation.
Brown
M F
MF
Department of Chemistry, University of Arizona, Tucson 85721.
D000818:Animals; D008051:Lipid Bilayers; D008968:Molecular Conformation; D010743:Phospholipids / Q000737:chemistry / Q000502:physiology; D010786:Photoreceptor Cells / Q000502:physiology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012243:Rhodopsin / Q000737:chemistry* / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology
D008051:Lipid Bilayers; D010743:Phospholipids; D012243:Rhodopsin