CRYSTALLOGRAPHIC ANALYSIS OF PROTEIN PHOSPATASE 2A

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 可逆的Ser/Thr蛋白磷酸化是细胞调节的基本机制。虽然在人类基因组中已鉴定出400多种丝氨酸/苏氨酸磷酸酶，但只有少数催化亚基存在于人类基因组中。蛋白磷酸酶2A(PP2A)是丝氨酸/苏氨酸磷酸酶的一个重要家族，与PP1一起，占大多数组织和细胞中丝氨酸/苏氨酸磷酸酶活性的90%。PP2A的解除调控与乳腺癌、肺癌和结直肠癌以及阿尔茨海默病、S病以及对病毒和寄生虫感染的易感性有关。一个典型的PP2A全酶(~160kD)由一个骨架A亚基、一个催化C亚基和一个调控B亚基组成，B亚基分为B、B？和B？家族。尽管许多实验室做出了巨大努力，但只确定了A亚基的结构。我们现在已经结晶了一种AB‘C杂三聚体络合物，它的衍射率可达~3.5°。我们想申请SSRL的光束时间，以确定这一至关重要的蛋白质复合体的晶体结构。

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.