CRYSTAL STRUCTURE DETERMINATION OF A BACTERIAL HOMOLOG OF HUMAN GAMMA-SECRETASE

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。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他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所在的机构。 人类γ-分泌酶在体内起着许多重要的作用：它是在一些家族性阿尔茨海默病中发生突变的酶，但它的正常功能也是身体正常功能所必需的，例如发育。 这种酶催化一种非常不寻常的反应，膜内蛋白水解，我们目前对其机制知之甚少。 部分挑战是由于我们不知道这种酶的结构，很难解决膜蛋白的结构。 为了克服这个问题，我们求助于该酶的细菌同系物，现在我们已经获得了细菌蛋白的衍射晶体。我们计划从这些晶体中收集x射线衍射数据，并解决这种膜蛋白的结构。 这项工作很可能阐明膜内蛋白水解的机制，并使我们能够了解影响这种机制的变化如何导致阿尔茨海默病。

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. The human gamma-secretase plays a number of important roles in the body: it is the enzyme that becomes mutated in some familial Alzheimer's disease but its proper function is also required for the normal function of the body, such as development. This enzyme catalyzes a very unusual reaction, intramembrane proteolysis, of which we currently know very little about its mechanism. Part of the challenge is due to the fact that we do not know the structure of this enzyme and it is difficult to solve the structure of a membrane protein. To overcome this problem, we resorted to bacterial homologs of the enzyme and now we have obtained diffracting crystals of the bacterial protein. We plan to collect x-ray diffraction data from these crystals and solve the structure of this membrane protein. This work is likely to shed light on the mechanism of intramembrane proteolysis and allow us to understand how changes affecting this memchanism can cause Alzheimer's disease.