LIGHT-REGULATED RETINAL ENZYMES

光调节视网膜酶

• 批准号: 3263489
• 负责人: MARK W BITENSKY
• 金额: $ 26.29万
• 依托单位: UNIVERSITY OF CALIF-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1994-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3263489
• 关键词: G protein; active sites; biological information processing; calcium; calcium binding protein; chemical binding; cyclic GMP; enzyme complex; enzyme mechanism; guanosine diphosphate; guanosine triphosphate; light adaptations; molecular site; phosphodiesterases; photolysis; receptor sensitivity; retina; rhodopsin; rod cell; transducin

Long term objectives: 1) Identify and describe the complete set of gene products and cofactors which support and regulate the explosive light activation of photoreceptor phosphodiesterase. 2) Understand the significance of this pathway for the events of visual excitation and its relevance for more general mechanisms of transmembrane signal transduction. 3) Understand the protein conformational dynamics which provide the essential molecular infrastructure of transmembrane signaling. Study the genetic basis of the homology between light activated PDE and hormone responsive adenylate cyclase; thereby evaluate the postulated role of 'exon shuffling' in gene evolution and gene structure. Specific Aims: 1) Identify the biochemical species and processes which support the light activation of photoreceptor PDE. 2) Describe photoreceptor Ca2+ transport processes and define the roles of PDE-mediated cGMP hydrolysis, H+/Ca2+ exchange, and disk lipids such as GD3 and IP3 in the process of visual excitation. 3) Develop a comprehensive theoretical model which explains the rod electrical response in terms of the biochemical and ionic processes that produce it. 4) Study the sequence and nature of light induced macromolecular conformational changes, and subunit interactions using biochemical and biophysical techniques. 5) Screen human chromosome specific libraries for genes which share exons with rhodopsin; translate and characterize the putative receptor gene products. Health relevance: The proposed studies address basic questions of significance for endocrinology, metabolic regulation of cellular processes, sensory signal transduction, neurophysiology and the evolution and expression of genes. The studies have relevance for endocrinology, ophthamology, neurology, cardiology and oncology. Methodology: The proposed studies employ the methods of analytical biochemistry, enzymology, neutron scattering, x-ray crystallography, membrane biophysics, electrophysiology, nuclear magnetic resonance spectroscopy, theoretical modeling and molecular biology including recombinant DNA and cloning techniques.

长期目标：1)识别和描述完整的基因集合