Ligand Binding Mechanisms in Human Cone Visual Pigments. Issue 7 (July 2019)

• Record Type: Journal Article
• Authors: Srinivasan, Sundaramoorthy; Guixà-González, Ramon; Cordomí, Arnau; Garriga, Pere
• Is Part Of: Trends in biochemical sciences. Volume 44:Issue 7(2019)
• Page Start: 629
• Page End: 639
• Publication Date: 2019-07
• Subjects: vision -- opsin -- retinoids -- ligand-binding site -- chromophore regeneration -- G protein-coupled receptor -- allostery -- color blindness; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2019.02.001
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : Vertebrate vision starts with light absorption by visual pigments in rod and cone photoreceptor cells of the retina. Rhodopsin, in rod cells, responds to dim light, whereas three types of cone opsins (red, green, and blue) function under bright light and mediate color vision. Cone opsins regenerate with retinal much faster than rhodopsin, but the molecular mechanism of regeneration is still unclear. Recent advances in the area pinpoint transient intermediate opsin conformations, and a possible secondary retinal-binding site, as determinant factors for regeneration. In this Review, we compile previous and recent findings to discuss possible mechanisms of ligand entry in cone opsins, involving a secondary binding site, which may have relevant functional and evolutionary implications. Highlights: Recent reports on the ligand-binding mechanisms of cone visual pigments identified transient conformations with concerted dynamics prior to regeneration with 11- cis -retinal. A secondary retinal-binding site has been identified in cone visual pigments. The retinal at this allosteric site could act as a buffer facilitating the maintenance of ligand-bound species. The novel results support the view that the actual stability of opsins may be the result of the combined effect of the conformational dynamics of the ligand-free opsins and the potential regulatory effects of the second retinal binding. Retinal analogs, such as 9- cis -retinal, have a clear differential effect on the regeneration mechanism of cone opsins. The combination of retinal analogs with other small molecules can be an interesting approach for the treatment of congenital retinal disorders.