TAILIEUCHUNG - Báo cáo khoa học: Alterations in the photoactivation pathway of rhodopsin mutants associated with retinitis pigmentosa

The visual photoreceptor rhodopsin undergoes a series of conformational changes upon light activation, eventually leading to the active metarhodop-sin II conformation, which is able to bind and activate the G-protein, transducin. | IFEBS Journal Alterations in the photoactivation pathway of rhodopsin mutants associated with retinitis pigmentosa Laia Bosch-Presegué1 Eva Ramon1 Darwin Toledo1 Arnau Cordomi2 and Pere Garriga1 1 Departament d Enginyeria Quimica Centre de Biotecnologia Molecular Universitat Politècnica de Catalunya Terrassa Spain 2 Laboratori de Medicina Computacional Unitat de Bioestadistica Facultat de Medicina Universitat Autonoma de Barcelona Cerdanyola del Valles Spain Keywords altered equilibrium metarhodopsin II photointermediate stability retinal degeneration visual diseases Correspondence P. Garriga Departament d Enginyeria Quimica Universitat Politecnica de Catalunya 08222 Terrassa Catalonia Spain Fax 34 937398225 Tel 34 937398568 E-mail Present address Chromatin Biology Laboratory Cancer Epigenetics and Biology Program PEBC I DIBELL Barcelona Catalonia Spain Received 23 November 2010 revised 1 February 2011 accepted 23 February 2011 doi The visual photoreceptor rhodopsin undergoes a series of conformational changes upon light activation eventually leading to the active metarhodopsin II conformation which is able to bind and activate the G-protein transducin. We have previously shown that mutant rhodopsins G51V and G89D associated with retinitis pigmentosa present photobleaching patterns characterized by the formation of altered photointermediates whose nature remained obscure. Our current detailed UV-visible spectroscopic analysis together with functional characterization indicate that these mutations influence the relative stability of the different metarhodopsin photointermediates by altering their equilibria and maintaining the receptor in a nonfunctional light-induced conformation that may be toxic to photoreceptor cells. We propose that G51V and G89D shift the equilibrium from metarhodopsin I towards an intermediate recently named as metarhodopsin Ib proposed to interact with transducin without activating it. .

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