CRYSTALLOGRAPHIC ANALYSIS OF PROTEIN PHOSPATASE 2A

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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.