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Structural Evidence for Visual Arrestin Priming Via Complexation of Phosphoinositols

Abstract

Visual arrestin (Arr1) terminates rhodopsin signaling by blocking its interaction with transducin. To do this, Arr1 translocates from the inner to the outer segment of photoreceptors upon light stimulation. Mounting evidence indicates that inositol phosphates (InsPs) affect Arr1 activity, but the Arr1-InsP molecular interaction remains poorly defined. We report the structure of bovine Arr1 in a ligand-free state featuring a near-complete model of the previously unresolved C-tail, which plays a crucial role in regulating Arr1 activity. InsPs bind to the N-domain basic patch thus displacing the C-tail, suggesting that they prime Arr1 for interaction with rhodopsin and help direct Arr1 translocation. These structures exhibit intact polar cores, suggesting that C-tail removal by InsP binding is insufficient to activate Arr1. These results show how Arr1 activity can be controlled by endogenous InsPs in molecular detail.

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References
1.
Langlois G, Chen C, Palczewski K, Hurley J, Vuong T . Responses of the phototransduction cascade to dim light. Proc Natl Acad Sci U S A. 1996; 93(10):4677-82. PMC: 39338. DOI: 10.1073/pnas.93.10.4677. View

2.
Imamoto Y, Tamura C, Kamikubo H, Kataoka M . Concentration-dependent tetramerization of bovine visual arrestin. Biophys J. 2003; 85(2):1186-95. PMC: 1303236. DOI: 10.1016/S0006-3495(03)74554-8. View

3.
Coffa S, Breitman M, Spiller B, Gurevich V . A single mutation in arrestin-2 prevents ERK1/2 activation by reducing c-Raf1 binding. Biochemistry. 2011; 50(32):6951-8. PMC: 3153575. DOI: 10.1021/bi200745k. View

4.
Zhuang T, Vishnivetskiy S, Gurevich V, Sanders C . Elucidation of inositol hexaphosphate and heparin interaction sites and conformational changes in arrestin-1 by solution nuclear magnetic resonance. Biochemistry. 2010; 49(49):10473-85. PMC: 3074303. DOI: 10.1021/bi101596g. View

5.
Hayashi F, Amakawa T . Light-mediated breakdown of phosphatidylinositol-4,5-bisphosphate in isolated rod outer segments of frog photoreceptor. Biochem Biophys Res Commun. 1985; 128(2):954-9. DOI: 10.1016/0006-291x(85)90139-1. View