Structure of the Rhodopsin/Transducin Complex

视紫红质/转导蛋白复合物的结构

• 批准号: 6886579
• 负责人: NED C VAN EPS
• 金额: $ 4.73万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6886579
• 关键词: conformation; electron spin resonance spectroscopy; mutant; postdoctoral investigator; protein protein interaction; protein structure function; receptor binding; rhodopsin; structural biology; transducin

DESCRIPTION (provided by applicant): G-protein coupled receptors (GPCRs) are a large superfamily of integral membrane proteins that transfer signals, via G-proteins, to downstream effectors. Detailed molecular information about how GPCRs activate their respective G-proteins is often lacking. Rhodopsin, a photoreceptor in the retina, defines the largest subfamily of GPCRs. As such, it acts as a paradigm for other receptors. Aberrations in rhodopsin's ability to couple to transducin (its G-protein) have been implicated in disease. The studies proposed here will provide direct structural information about the rhodopsin/transducin complex. Site-directed spin labeling (SDSL) experiments on both rhodopsin and transducin (Gt) will reveal regions of conformational change due to their mutual interaction. It is one goal of this proposal to identify areas of conformational change within transducin that are important for GDP release. Detailed analysis of these structural changes is expected to provide a mechanistic model for the rhodopsin catalyzed nucleotide exchange within Gt. Additionally, distance measurements will be made to map the binding site of transducin on rhodopsin. Collectively, these experiments will provide detailed structural information about the rhodopsin/transducin complex.

描述（由申请人提供）： G蛋白偶联受体（GPCR）是一个大的膜蛋白超家族，通过G蛋白将信号传递到下游效应器。关于GPCR如何激活其各自的G蛋白的详细分子信息往往缺乏。视紫红质是视网膜中的光感受器，定义了GPCR的最大亚家族。因此，它作为其他受体的范例。视紫红质与转导素（其G蛋白）偶联的能力异常与疾病有关。本文的研究将提供有关视紫红质/转导素复合物的直接结构信息。视紫红质和转导素（Gt）的定点自旋标记（SDSL）实验将揭示由于它们的相互作用而导致的构象变化区域。这是一个目标的建议，以确定领域的构象变化内transducin是重要的GDP释放。这些结构变化的详细分析，预计将提供一个机制模型的视紫红质催化的核苷酸交换内的G。此外，距离测量将进行映射的结合位点的transducin视紫红质。总的来说，这些实验将提供有关视紫红质/转导素复合物的详细结构信息。