BIOLOGICAL FUNCTIONS OF HUMAN CD38 BY HIGH PRESSURE X-RAY CRYSTALLOGRAPHY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 人CD 38是一种参与多种抗原和生理功能的膜蛋白。在白细胞的细胞膜上，这种蛋白质非常灵活，可以与其他细胞表面分子相互作用，引发导致细胞增殖、分化和程序性细胞死亡的信号事件。此外，人CD 38是胞外酶，可以合成和水解能够动员钙离子的环核苷酸。 测定了人CD 38胞外区的晶体结构。然而，在结构上尚不清楚这种酶如何与其他细胞分子进行信号传导。在这项研究中，我们建议使用高压作为外力来使蛋白质处于结晶状态。通过探索CD 38晶体上的一系列压力（从1个大气压到~ 10，000个大气压），我们期望表征蛋白质结构可塑性/柔性的动态行为。此外，我们还期望利用这种外力作为一种工具，机械地探测生物反应，否则逃避调查。

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. Human CD38 is a membrane protein involved in versatile antigenic and physiological functions. On the cell membrane of leukocytes, this protein is very flexible and can interact with other cell surface molecules to elicit signal events resulting in cell proliferation, differentiation, and programmed cell death. Besides, human CD38 is an ectoenzyme and can synthesize and hydrolyze a cyclic nucleotide capable of mobilizing calcium ions. The crystal structure of human CD38 extracellular domain has been determined. However, it is structurally unknown how this enzyme communicates with other cellular molecules towards signaling. In this study, we propose to use high pressure as an external force to tantalize the protein in its crystalline state. By exploring a series of pressure (from 1 atmosphere to ~10,000 atmosphere) on CD38 crystals, we expect to characterize the dynamic behavior of the protein's structural plasticity/flexibility. Besides, we also expect to use this external force as a tool to mechanistically probe biological reactions that otherwise evade from investigation.