Binding Specificity of Retinal Analogs to Photoactivated Visual Pigments Suggest Mechanism for Fine-Tuning GPCR-Ligand Interactions
| Autor: | Eva Ramon, Arnau Cordomí, Sundaramoorthy Srinivasan, Pere Garriga |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Rhodopsin
Opsin Light genetic structures Clinical Biochemistry Molecular Dynamics Simulation Biology Ligands Biochemistry Receptors G-Protein-Coupled chemistry.chemical_compound Isomerism Chlorocebus aethiops Drug Discovery Animals Humans Regeneration Transducin Molecular Biology Binding selectivity G protein-coupled receptor Pharmacology Binding Sites Retinal General Medicine Ligand (biochemistry) Receptor–ligand kinetics Protein Structure Tertiary Kinetics chemistry COS Cells Retinaldehyde biology.protein Biophysics Molecular Medicine Cattle sense organs Signal transduction Retinal Pigments Protein Binding |
| Zdroj: | Chemistry & Biology. 21(3):369-378 |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/j.chembiol.2014.01.006 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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