The focus of this proposal is on the structure and function of the visual pigment rhodopsin. There are two Specific Aims: 1. The 3-dimensional crystallization and x-ray structure determination of recombinant wild-type and mutant rhodopsins. While the x-ray crystal structure of bovine rhodopsin was solved several years ago, the protein used in that study was isolated from native sources. No one has as yet crystallized rhodopsin from a recombinant source. This is an important goal because once achieved it will allow a high resolution structural analysis of rhodopsin mutants. Structural analysis of rhodopsin mutants is a crucial next step for a fundamental understanding of the functioning of this protein. The mutants of greatest interest in this work will be those found in the retinal diseases retinitis pigmentosa and congenital night blindness, specifically those that constitutively activate the protein. 2. To use transgenic Xenopus laevis to explore the molecular mechanisms of retinal disease arising from mutations in the genes for rhodopsin and its downstream signaling component transducin. The main focus of this Aim will be on the disease, retinitis pigmentosa.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1-VISC (01))
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Mariani, Andrew P
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Brandeis University
Schools of Arts and Sciences
United States
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