Experimental Evidence for Specificity in Rhodopsin‐Lipid Interactions

It is well known that efficiency of the rhodopsin‐dependent steps of the visual process is exquisitely sensitive to membrane lipid composition, in particular to the content of polyunsaturated docosahexaenoic acid (DHA). Current theories interpreted this sensitivity exclusively as a consequence of changes in continuum elastic properties of the lipid matrix. Here we investigated if specific interactions between DHA‐containing lipids and rhodopsin may contribute to the effect. By proton MAS NMR with saturation transfer from protein to lipids (ST‐NMR)(1) we observed strongest interactions between rhodopsin with DHA‐containing phosphatidylethanolamines (PE). This observation is supported by results from deuterium NMR experiments which show that PEs are enriched in the first layer of lipids surrounding rhodopsin. The rhodopsin surface is heterogeneous, with sites for specific interaction with DHA‐containing lipids.(2) When lipids interact with a protein at a particular site, they could alter interactions within the protein, e.g. interaction between transmembrane helices in GPCR that are linked to receptor activation. Furthermore, the specific interactions with particular lipid species may generate a unique microenvironment for the protein with altered membrane continuum properties.