THE STRUCTURE OF FULL LENGTH HUMAN ANNEXIN I IN COMPLEX WITH CALCIUM AND PHOSPHA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。膜联蛋白是一种可溶性蛋白，以钙依赖的方式与带负电荷的磷脂结合。膜联蛋白家族的每个成员都由两个主要结构域组成：一个保守的羧基末端蛋白核心和一个氨基末端，该氨基末端对于该家族的特定成员来说是唯一的，可以指定单个膜联蛋白的特性。已经解决了几个高分辨率晶体膜联蛋白结构（包括膜联蛋白I）；然而，没有一个已发表的膜联蛋白结构包含一个完整的n端结构域。目前，我们已经能够表达、纯化和结晶全长人膜联蛋白I。通过求解全长人膜联蛋白I的结构，我们希望得到更多关于n端结构域如何与核心结构域相互作用的信息。此外，我们希望获得一些关于膜联蛋白家族成员如何参与膜相关过程（包括膜聚集和融合）的有用见解。我们认为人膜联蛋白I的结构构象在钙离子和磷酸盐离子的存在下会发生改变。我们希望通过解决天然全长人膜联蛋白I的结构，以及解决钙和磷酸盐离子存在下的全长人膜联蛋白I的结构来测试这种结构构象变化是否发生

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. Annexins are soluble proteins that bind to negatively charged phospholipids in a calcium dependent manner. Each member of the annexin family comprises of two principal domains: a conserved carboxyl terminal protein core and an amino terminal that is unique for a given member of the family that may specify individual annexin properties. Several high-resolution crystal annexin structures have been solved (including annexin I); however, none of the published annexin structures contain a complete N-terminal domain. Currently, we have been able to express, purify and crystallize full length human annexin I. By solving the structure of the full length human annexin I we hope to get more information on how the N-terminal domain interacts with the core domain. In addition, we hope to gain some useful insights on how this member of the annexin family is implicated in membrane related processes including membrane aggregation and fusion. We propose that the structural conformation of human annexin I will be altered in the presence of calcium and phosphate ions. We wish to test whether this structural conformational change occurs by not only solving the structure of native full length human annexin I, but also solving the full length human annexin I in the presence of calcium and phosphate ions