Functional role of positively selected amino acid substitutions in mammalian rhodopsin evolution
Visual rhodopsins are membrane proteins that function as light photoreceptors in the vertebrate retina. Specific amino acids have been positively selected in visual pigments during mammal evolution, which, as products of adaptive selection, would be at the base of important functional innovations. W...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/102267 |
| Acceso en línea: | https://hdl.handle.net/2117/102267 https://dx.doi.org/10.1038/srep21570 |
| Access Level: | acceso abierto |
| Palabra clave: | G proteins--Receptors DOMINANT RETINITIS-PIGMENTOSA VERTEBRATE VISUAL PIGMENTS DIM-LIGHT VISION RETINAL DEGENERATION MOLECULAR EVOLUTION BOVINE RHODOPSIN FLUORESCENCE SPECTROSCOPY TRANSDUCIN ACTIVATION LINKED GLYCOSYLATION MAXIMUM-LIKELIHOOD Proteïnes G -- Receptors Àrees temàtiques de la UPC::Ciències de la salut::Medicina |
| Sumario: | Visual rhodopsins are membrane proteins that function as light photoreceptors in the vertebrate retina. Specific amino acids have been positively selected in visual pigments during mammal evolution, which, as products of adaptive selection, would be at the base of important functional innovations. We have analyzed the top candidates for positive selection at the specific amino acids and the corresponding reverse changes (F13M, Q225R and A346S) in order to unravel the structural and functional consequences of these important sites in rhodopsin evolution. We have constructed, expressed and immunopurified the corresponding mutated pigments and analyzed their molecular phenotypes. We find that position 13 is very important for the folding of the receptor and also for proper protein glycosylation. Position 225 appears to be important for the function of the protein affecting the G-protein activation process, and position 346 would also regulate functionality of the receptor by enhancing G-protein activation and presumably affecting protein phosphorylation by rhodopsin kinase. Our results represent a link between the evolutionary analysis, which pinpoints the specific amino acid positions in the adaptive process, and the structural and functional analysis, closer to the phenotype, making biochemical sense of specific selected genetic sequences in rhodopsin evolution. |
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