The long-term goal of this proposal is to understand the structures and activation of mechanisms of rod and cone pigments. Several mutations in rhodopsin, the rod pigment, have been shown to result in gain or loss of function and ultimately lead to retinal degeneration. However, similar degenerative diseases have not been reported from cone pigment mutations. The dearth of information on cone pigments or inherent differences of cone pigment structure and/or activation are two possible reasons. More data on the basic properties of bone pigments will shed light on eith4r scenario. This proposal is directed at determining the important protein-ligand interactions, particularly around the 9-methyl group of 11-cis retinal, in the activation and inactivation of rod and cone pigments. There are three aims to this proposal: (1) establishment of a light-independent active form of a cone pigment consistent with a """"""""steric trigger"""""""" mechanism involving amino acids different from those previously published by others; (2) test of the """"""""salt bridge"""""""" model of activation in the cone pigments; (3) determination of the role of the extracellular domains on the stability and activation of visual pigments. Spectroscopic and transducin activity measurements of expressed salamander visual pigments will be used. These results will also be important in the understanding of the activation mechanisms of the larger field of G protein-coupled receptors.
| Kono, Masahiro; Goletz, Patrice W; Crouch, Rosalie K (2008) 11-cis- and all-trans-retinols can activate rod opsin: rational design of the visual cycle. Biochemistry 47:7567-71 |
| McKee, Timothy D; Lewis, Margaret R; Kono, Masahiro (2007) Engineering a ""steric doorstop"" in rhodopsin: converting an inverse agonist to an agonist. Biochemistry 46:12248-52 |
| Ablonczy, Zsolt; Kono, Masahiro; Knapp, Daniel R et al. (2006) Palmitylation of cone opsins. Vision Res 46:4493-501 |
| Lewis, Margaret R; Kono, Masahiro (2006) Rhodopsin deactivation is affected by mutations of Tyrl91. Photochem Photobiol 82:1442-6 |
| Kono, Masahiro (2006) Constitutive activity of a UV cone opsin. FEBS Lett 580:229-32 |
| Isayama, T; Chen, Y; Kono, M et al. (2006) Differences in the pharmacological activation of visual opsins. Vis Neurosci 23:899-908 |
| Sutton, R Bryan; Vishnivetskiy, Sergey A; Robert, Justin et al. (2005) Crystal structure of cone arrestin at 2.3A: evolution of receptor specificity. J Mol Biol 354:1069-80 |
| Kono, Masahiro; Crouch, Rosalie K; Oprian, Daniel D (2005) A dark and constitutively active mutant of the tiger salamander UV pigment. Biochemistry 44:799-804 |
| Kefalov, Vladimir J; Estevez, Maureen E; Kono, Massahiro et al. (2005) Breaking the covalent bond--a pigment property that contributes to desensitization in cones. Neuron 46:879-90 |
| Das, Joydip; Crouch, Rosalie K; Ma, Jian-xing et al. (2004) Role of the 9-methyl group of retinal in cone visual pigments. Biochemistry 43:5532-8 |
