TY - JOUR
T1 - Binding specificity of retinal analogs to photoactivated visual pigments suggest mechanism for fine-tuning GPCR-ligand interactions
AU - Srinivasan, Sundaramoorthy
AU - Ramon, Eva
AU - Cordomí, Arnau
AU - Garriga, Pere
PY - 2014/3/20
Y1 - 2014/3/20
N2 - 11-cis-retinal acts as an inverse agonist stabilizing the inactive conformation of visual pigments, and upon photoactivation, it isomerizes to all-trans-retinal, initiating signal transduction. We have analyzed opsin regeneration with retinal analogs for rhodopsin and red cone opsin. We find differential binding of the analogs to the receptors after photobleaching and a dependence of the binding kinetics on the oligomerization state of the protein. The results outline the sensitivity of retinal entry to the binding pocket of visual receptors to the specific conformation adopted by the receptor and by the molecular architecture defined by specific amino acids in the binding pocket and the retinal entry site, as well as the topology of the retinal analog. Overall, our findings highlight the specificity of the ligand-opsin interactions, a feature that can be shared by other G-protein-coupled receptors. © 2014 Elsevier Ltd.
AB - 11-cis-retinal acts as an inverse agonist stabilizing the inactive conformation of visual pigments, and upon photoactivation, it isomerizes to all-trans-retinal, initiating signal transduction. We have analyzed opsin regeneration with retinal analogs for rhodopsin and red cone opsin. We find differential binding of the analogs to the receptors after photobleaching and a dependence of the binding kinetics on the oligomerization state of the protein. The results outline the sensitivity of retinal entry to the binding pocket of visual receptors to the specific conformation adopted by the receptor and by the molecular architecture defined by specific amino acids in the binding pocket and the retinal entry site, as well as the topology of the retinal analog. Overall, our findings highlight the specificity of the ligand-opsin interactions, a feature that can be shared by other G-protein-coupled receptors. © 2014 Elsevier Ltd.
U2 - 10.1016/j.chembiol.2014.01.006
DO - 10.1016/j.chembiol.2014.01.006
M3 - Article
VL - 21
SP - 369
EP - 378
IS - 3
ER -