title: Binding specificity of retinal analogs to photoactivated visual pigments suggest mechanism for fine-tuning GPCR-ligand interactions.
abstract: 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.
authors.affiliation: Chemical Engineering Department, Grup de Biotecnologia Molecular i Industrial, Centre de Biotecnologia Molecular, Universitat Politècnica de Catalunya, Edifici Gaia, Rambla de Sant Nebridi 22, 08222 Terrassa, Catalonia, Spain.
authors.forename: Sundaramoorthy
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Chemical Engineering Department, Grup de Biotecnologia Molecular i Industrial, Centre de Biotecnologia Molecular, Universitat Politècnica de Catalunya, Edifici Gaia, Rambla de Sant Nebridi 22, 08222 Terrassa, Catalonia, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Ramon
authors.affiliation: Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Arnau
authors.initials: A
authors.lastname: Cordomí
authors.affiliation: Chemical Engineering Department, Grup de Biotecnologia Molecular i Industrial, Centre de Biotecnologia Molecular, Universitat Politècnica de Catalunya, Edifici Gaia, Rambla de Sant Nebridi 22, 08222 Terrassa, Catalonia, Spain. Electronic address: pere.garriga@upc.edu.
authors.forename: Pere
authors.initials: P
authors.lastname: Garriga
mesh_terms: D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002417:Cattle; D002522:Chlorocebus aethiops; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D008024:Ligands; D008027:Light; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration; D012168:Retinal Pigments / Q000378:metabolism*; D012172:Retinaldehyde / Q000031:analogs & derivatives / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015293:Transducin / Q000378:metabolism
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D012168:Retinal Pigments; D012243:Rhodopsin; D015293:Transducin; D012172:Retinaldehyde