MOLECULAR MECHANISMS OF CNG CHANNEL FUNCTION

CNG通道功能的分子机制

• 批准号: 6948893
• 负责人: ARIELA GORDON-SHAAG
• 金额: $ 4.83万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6948893
• 关键词: SDS polyacrylamide gel electrophoresis; Xenopus oocyte; binding sites; biochemistry; biological signal transduction; chromophore; crosslink; cyclic GMP; electrophysiology; molecular genetics; photoactivation; polymerase chain reaction; postdoctoral investigator; protein protein interaction; protein structure; protein structure function; rhodopsin; sensory receptors; site directed mutagenesis; visual phototransduction; western blottings

DESCRIPTION (provided by applicant): Visual transduction begins with absorption of a photon by rhodopsin. Photoisomerization of the chromophore must somehow signal the photoreceptor synapse to alter its release of transmitter onto second-order neurons. This signal is produced by the cyclic GMP- activated ion channel. This ion channel then converts the signal of light into an electrical signal the brain can understand. This proposal focuses on cGMP-activated ion channels. I will examine structural rearrangements that occur in response to cGMP that are coupled to channel activation. I will use the following tools to study how this protein works; electrical recordings, to assay the flux of ions through the pore of the protein; molecular biology to alter the amino acid sequence of the protein and test specific models of its function; and protein chemistry to study interactions between domains of the proteins, between subunits, and between the channels and other cellular proteins. Through these experiments I expect to gain significant insight into how the cGMP-activated ion channels function during visual transduction.

描述（由申请人提供）：视觉转导始于视紫红质吸收光子。发色团的光异构化必须以某种方式向光感受器突触发出信号，以改变其向二级神经元释放递质。该信号由循环 GMP 激活的离子通道产生。然后，该离子通道将光信号转换为大脑可以理解的电信号。该提案重点关注 cGMP 激活的离子通道。我将检查与通道激活相关的 cGMP 响应而发生的结构重排。我将使用以下工具来研究这种蛋白质的工作原理；电记录，测定通过蛋白质孔的离子通量；分子生物学改变蛋白质的氨基酸序列并测试其功能的特定模型；和蛋白质化学，研究蛋白质结构域之间、亚基之间以及通道与其他细胞蛋白质之间的相互作用。通过这些实验，我希望能够深入了解 cGMP 激活的离子通道在视觉转导过程中如何发挥作用。