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O.G. Kisselev, J.H. McDowell, P.A. Hargrave; Arrestin Binding Triggers Specific Conformational Changes in the C-terminus of Phosphorylated Rhodopsin . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3263.
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Visual arrestin binds to the phosphorylated carboxy-terminus of rhodopsin to block ineractions with transducin and terminate signaling in the rod photoreceptor cells. Interactions between arrestin and phospho-rhodopsin are accompanied by a conformational rearrangement in arrestin, but whether complementary conformational changes occur in the phosphorylated C-terminus of rhodopsin is unclear. A synthetic peptide that represents a Rh(330-348) region of bovine rhodopsin, phosphorylated at all seven positions (7PP), has been shown to bind arrestin and mimic inhibition of signal transduction. In this study, we examine conformational changes in this synthetic peptide upon binding to arrestin by high-resolution proton Transferred Nuclear Overhauser Effect Spectroscopy. We show that 7PP is completely disordered in solution, but becomes structured upon binding to arrestin. A control, unphosphorylated peptide that fails to bind to arrestin remains highly disordered under the same experimental conditions. Specific NMR distance constraints are used to model the arrestin-bound conformation of the phosphorylated carboxy-terminus of rhodopsin. The models suggest a molecular mechanism by which arrestin occludes the transducin-binding site leading to the quenching of phototransduction. This work is supported by Norman J. Stupp Foundation and NIH GM63203 (to O.G.K.), and NIH EY06225 and award from Research to Prevent Blindness (to P.A.H).
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