CONFORMATIONAL CHANGES IN ACTIN

肌动蛋白的构象变化

• 批准号: 6598648
• 负责人: ROBERT J FLETTERICK
• 金额: $ 22.57万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6598648
• 关键词: SDS polyacrylamide gel electrophoresis; X ray crystallography; actin binding protein; actins; active sites; adenosine triphosphate; binding sites; calorimetry; conformation; cytoskeleton; light scattering; mass spectrometry; microfilaments; polymers; protein protein interaction; structural biology; troponin

DESCRIPTION (provided by applicant): Actin is a major cytoskeletal protein critical for cellular motility and mechanical strength, protein sorting and secretion, signal transduction and cell division. Since most of these functions are related to the properties of filamentous polymers of actin, F-actin, understanding of the dynamics of actin filament assembly and its structure is vital. The dynamic process of actin polymerization utilizes the ability of actin to hydrolyze ATP in its active site and to undergo nucleotide-dependent conformational transitions that influence filament dynamics. To date, details of F-actin structure and the mechanism of nucleotide-induced structural transitions in the filament are not yet known. The goal of this proposal is to elucidate details of the structure of F-actin at the atomic-resolution level. Furthermore, we would like to understand the mechanism of nucleotide-dependent structural changes within F-actin and how this mechanism controls binding interactions of actin with regulatory proteins. The actin filament network is associated with numerous diseases and abnormalities including the abnormal growth properties and metastatic potential of tumor cells. Therefore, results of this study would create the long anticipated structural background for developing new therapeutics targeting the actin cytoskeleton.

描述（由申请人提供）：肌动蛋白是一种主要的细胞骨架蛋白，对于细胞运动和机械强度、蛋白质分选和分泌、信号转导和细胞分裂至关重要。由于大多数这些功能与肌动蛋白丝状聚合物（F-肌动蛋白）的特性有关，因此了解肌动蛋白丝组装的动力学及其结构至关重要。肌动蛋白聚合的动态过程利用了肌动蛋白在其活性位点水解 ATP 的能力，并经历影响丝动力学的核苷酸依赖性构象转变。迄今为止，F-肌动蛋白结构的细节和丝中核苷酸诱导的结构转变的机制尚不清楚。 该提案的目标是在原子分辨率水平上阐明 F-肌动蛋白结构的细节。此外，我们希望了解 F-肌动蛋白内核苷酸依赖性结构变化的机制，以及该机制如何控制肌动蛋白与调节蛋白的结合相互作用。 肌动蛋白丝网络与许多疾病和异常相关，包括肿瘤细胞的异常生长特性和转移潜力。因此，这项研究的结果将为开发针对肌动蛋白细胞骨架的新疗法创造期待已久的结构背景。