Conformational Energetics of Rhodopsin Modulated by Nonlamellar-Forming Lipids
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- 作者：Ana Vitó ; ria Botelho ; Nicholas J. Gibson ; Robin L. Thurmond ; Yin Wang ; and Michael F. Brown
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：May 21, 2002
- 年：2002
- 卷：41
- 期：20
- 页码：6354 - 6368
- 全文大小：190K
- 年卷期：v.41,no.20(May 21, 2002)
- ISSN：1520-4995
文摘
Rhodopsin is an important example of a G protein-coupled receptor (GPCR) in which 11-cis-retinal is the ligand and acts as an inverse agonist. Photolysis of rhodopsin leads to formation of theactivated meta II state from its precursor meta I. Various mechanisms have been proposed to explain howthe membrane composition affects the meta I-meta II conformational equilibrium in the visual process.For rod disk membranes and recombinant membranes containing rhodopsin, the lipid properties havebeen discussed in terms of elastic deformation of the bilayer. Here we have investigated the relation ofnonlamellar-forming lipids, such as dioleoylphosphatidylethanolamine (DOPE), together with dioleoylphosphatidylcholine (DOPC), to the photochemistry of membrane-bound rhodopsin. We conducted flashphotolysis experiments for bovine rhodopsin recombined with DOPE/DOPC mixtures (0:100 to 75:25) asa function of pH to explore the dependence of the photochemical activity on the monolayer curvaturefree energy of the membrane. It is well-known that DOPC forms bilayers, whereas DOPE has a propensityto adopt the nonlamellar, reverse hexagonal (HII) phase. In the case of neutral DOPE/DOPC recombinants,calculations of the membrane surface pH confirmed that an increase in DOPE favored the meta II state.Moreover, doubling the PE headgroup content versus the native rod membranes substituted for thepolyunsaturated, docosahexaenoic acyl chains (22:6
3), suggesting rhodopsin function is associated witha balance of forces within the bilayer. The data are interpreted by applying a flexible surface model, inwhich the meta II state is stabilized by lipids tending to form the HII phase, with a negative spontaneouscurvature. A simple theory, based on principles of surface chemistry, for coupling the energetics ofmembrane proteins to material properties of the bilayer lipids is described. For rhodopsin, the free energybalance of the receptor and the lipids is altered by photoisomerization of retinal and involves curvaturestress/strain of the membrane (frustration). A new biophysical principle is introduced: matching of thespontaneous curvature of the lipid bilayer to the mean curvature of the lipid/water interface adjacent tothe protein, which balances the lipid/protein solvation energy. In this manner, the thermodynamic drivingforce for the meta I-meta II conformational change of rhodopsin is tightly controlled by mixtures ofnonlamellar-forming lipids having distinctive material properties.
3), suggesting rhodopsin function is associated witha balance of forces within the bilayer. The data are interpreted by applying a flexible surface model, inwhich the meta II state is stabilized by lipids tending to form the HII phase, with a negative spontaneouscurvature. A simple theory, based on principles of surface chemistry, for coupling the energetics ofmembrane proteins to material properties of the bilayer lipids is described. For rhodopsin, the free energybalance of the receptor and the lipids is altered by photoisomerization of retinal and involves curvaturestress/strain of the membrane (frustration). A new biophysical principle is introduced: matching of thespontaneous curvature of the lipid bilayer to the mean curvature of the lipid/water interface adjacent tothe protein, which balances the lipid/protein solvation energy. In this manner, the thermodynamic drivingforce for the meta I-meta II conformational change of rhodopsin is tightly controlled by mixtures ofnonlamellar-forming lipids having distinctive material properties.