CRYSTALLOGRAPHIC ANALYSIS OF PROTEIN PHOSPATASE 2A

蛋白质磷酸酶 2A 的晶体分析

• 批准号: 7722055
• 负责人: Wenqing Xu
• 金额: $ 0.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7722055
• 关键词: Accounting; Alzheimer' s Disease; Breast; Catalytic Domain; Cells; Colorectal Cancer; Complex; Computer Retrieval of Information on Scientific Projects Database; Disease susceptibility; Family; Funding; Grant; Holoenzymes; Human Genome; Institution; Lung; Parasitic infection; Phosphoric Monoester Hydrolases; Phosphorylation; Phosphotransferases; Protein Analysis; Protein phosphatase; Proteins; Regulation; Research; Research Personnel; Resolution; Resources; Source; Structure; Tissues; United States National Institutes of Health; Viral; scaffold

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Reversible protein Ser/Thr phosphorylation is a fundamental mechanism for cell regulation. While more than 400 Ser/Thr kinases have been identified in the human genome, there are only a few catalytic subunits for Ser/Thr phosphatases. Protein phosphatase 2A (PP2A) is an essential family of Ser/Thr phosphatases that, together with PP1, accounts for >90% of Ser/Thr phosphatase activity in most tissues and cells. Deregulation of PP2A is associated with breast, lung, and colorectal cancers as well as Alzheimer?s Disease and susceptibility to viral and parasitic infection. A typical PP2A holoenzyme (~160 kD) contains a scaffold A subunit, a catalytic C subunit and one of many regulatory B subunits, which are divided into B, B? and B? families. Despite tremendous efforts from many labs, only the structure of the A subunit has been determined. We have now crystallized an AB'C heterotrimeric complex that diffracts to ~3.5 ¿ resolution. We would like to apply for the beamtime at SSRL, to determine the crystal structure of this critically important protein complex.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 可逆的蛋白质 Ser/Thr 磷酸化是细胞调节的基本机制。虽然人类基因组中已鉴定出 400 多种 Ser/Thr 激酶，但 Ser/Thr 磷酸酶的催化​​亚基却很少。蛋白磷酸酶 2A (PP2A) 是 Ser/Thr 磷酸酶的重要家族，与 PP1 一起占大多数组织和细胞中 Ser/Thr 磷酸酶活性的 90% 以上。 PP2A 的失调与乳腺癌、肺癌和结直肠癌以及阿尔茨海默病以及对病毒和寄生虫感染的易感性有关。典型的 PP2A 全酶（~160 kD）包含支架 A 亚基、催化 C 亚基和许多调节 B 亚基之一，这些亚基分为 B、B？和B？家庭。尽管许多实验室付出了巨大的努力，但仅确定了 A 亚基的结构。我们现已结晶出 AB'C 异三聚体复合物，其衍射分辨率约为 3.5 ¿我们想申请 SSRL 的 Beamtime，以确定这一极其重要的蛋白质复合物的晶体结构。