Study of AAA proteins by X-ray protein crystallography

X射线蛋白质晶体学研究AAA蛋白质

• 批准号: 7292876
• 负责人: di s xia
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7292876
• 关键词: Study; AAA; proteins; ray; protein

Intracellular protein degradation is a major post-translational regulatory mechanism and plays a crucial role in many vital cellular functions; it also serves to remove damaged, denatured, and other abnormal proteins. In collaboration with Dr. Maurizi at LCB, my group has determined the crystal structure of the full-length ClpA, the regulatory component of the ClpAP complex. As the first crystal structure of AAA+ protein to be determined with two AAA+ modules, the ClpA structure has provided insights into the structural basis for the functional difference of the two AAA+ modules. My group has also obtained the structure of the isolated N-domain of ClpA in complex with ClpS that is known to alter the substrate selectivity in ClpA, much like the adaptor proteins used by many other AAA+ proteins (Maurizi and Xia, 2004). We also defined the function of the ClpA N-terminal domain by analyzing crystallographically details of its multiple protein and peptide binding sites (Xia et al., 2004). Having obtained structures of all components in the ClpAPS system, our group is now focusing on obtaining structures of ClpA in various conformations induced by bound nucleotides, and on crystallizing binary complexes of ClpA with either ClpS or ClpP, as well as with various substrates.

细胞内蛋白质降解是一种主要的翻译后调节机制，在许多重要的细胞功能中发挥着至关重要的作用；它还可以去除受损、变性和其他异常蛋白质。我的团队与 LCB 的 Maurizi 博士合作，确定了全长 ClpA（ClpAP 复合物的调节成分）的晶体结构。作为第一个用两个 AAA+ 模块确定的 AAA+ 蛋白晶体结构，ClpA 结构为了解两个 AAA+ 模块的功能差异提供了结构基础。我的小组还获得了与 ClpS 复合的 ClpA 的分离 N 结构域的结构，已知 ClpS 可以改变 ClpA 中的底物选择性，非常类似于许多其他 AAA+ 蛋白使用的接头蛋白（Maurizi 和 Xia，2004）。我们还通过分析 ClpA N 端结构域的多个蛋白质和肽结合位点的晶体学细节来定义 ClpA N 端结构域的功能 (Xia 等人，2004)。在获得了 ClpAPS 系统中所有组件的结构后，我们小组现在专注于获得由结合核苷酸诱导的各种构象的 ClpA 结构，以及结晶 ClpA 与 ClpS 或 ClpP 以及与各种底物的二元复合物。