Insights from biophysical studies on the role of polyunsaturated fatty acids for function of G-protein coupled membrane receptors.
The composition of the lipid matrix is critical for function of membrane proteins. Perhaps one of the best studied examples is the function of the G-protein-coupled membrane receptor (GPCR) rhodopsin which is located in membranes with high content of phospholipids with polyunsaturated docosahexaenoic acid chains (DHA, 22:6n-3). Technological advances enabled a more detailed study of structure and dynamics of DHA chains and their interaction with rhodopsin. It was established that polyunsaturated DHA differs from saturated and monounsaturated hydrocarbon chains by far more rapid structural conversions. Furthermore, DHA chains tend to have higher density near the lipid/water interface while density of saturated chains is higher in the bilayer center. The interface of rhodopsin has a small number of sites for tighter interaction with DHA. Polyunsaturated phosphatidylethanolamines accumulate preferentially near the protein. Surprisingly, the high conformational freedom of most DHA chains is not measurably reduced upon interaction with rhodopsin. While some observations point at an involvement of continuum elastic properties of membranes in modulation of rhodopsin function, there is growing evidence for a role of weakly specific DHA-rhodopsin interactions.
Gawrisch
Klaus
K
Section of NMR, Laboratory of Membrane Biochemistry and Biophysics, NIAAA, NIH, Bethesda, MD 20892, USA. klausg@mail.nih.gov
Soubias
Olivier
O
Mihailescu
Mihaela
M
D000818:Animals; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000378:metabolism; D013329:Structure-Activity Relationship
D005231:Fatty Acids, Unsaturated; D043562:Receptors, G-Protein-Coupled; D004281:Docosahexaenoic Acids; D012243:Rhodopsin