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V.V. Gurevich, B.R. Sutton, S.A. Vishnivetskiy, D. Raman, J. Robert, S.M. Hanson, J. Navarro, B.E. Knox, M. Kono; Structure and Function of Cone Arrestin: Does Transient Binding to Cone Opsin Contribute to the Speed of Cone Recovery? . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1176.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Determine the structural basis and functional characteristics of cone arrestin interaction with phosphorylated cone opsins. Methods: Based on our X–ray crystal structure of Salamander cone arrestin at 2.3A, we introduced targeted mutations into putative phosphate–sensing elements of Salamander and human cone arrestins and tested the binding of wild type (WT) and mutant proteins to different functional forms of purified human green cone opsin, Xenopus cone pigment SWS2, bovine and frog rhodopsin, and m2 muscarinic cholinergic receptor. Results: Overall 3D structure of cone arrestin is very similar to that of other family members. The molecule consists of two domains, the relative positions of which in the basal state are held by the "polar core" (the main phosphate sensor) and three–element interaction between the C–tail, a–helix I, and b–strand I in the N–domain. Several structural features place cone arrestin between rod arrestin and non–visual members of arrestin family. WT cone arrestins demonstrate preferential binding to phosphorylated light–activated cone pigments, low binding to phosphorylated light–activated rhodopsin and active phosphorylated m2 receptor. Similar to other arrestin proteins, mutations that destabilize the polar core or the three–element interaction enhance its binding to phosphorylated and unphosphorylated active cone opsins. These mutations also compromise cone arrestin selectivity, enhancing its binding to rhodopsin and m2 receptor. The unique feature of cone arrestin is that the stability of its complex with cone opsins is substantially lower than that of the complexes of other arrestins with their cognate receptors. Cone arrestin specifically binds microtubules, suggesting that cytoskeleton interaction may drive its translocation away from the outer segment in the dark, similar to what we found in rods. Conclusions: Phosphate–sensing elements and their functional roles are conserved in cone arrestin. In other respects, structurally it is an evolutionary link between promiscuous non–visual arrestins and highly specialized rod arrestin. Transient interaction of cone arrestin with cone opsins correlates with rapid spontaneous decay of cone pigments and may play a role in fast recovery of cones in vivo that requires arrestin dissociation and opsin dephosphorylation.
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