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

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。 膜联蛋白是一种可溶性蛋白质，以钙依赖的方式与带负电荷的磷脂结合。Annexin家族的每个成员都由两个主要结构域组成：保守的羧基末端蛋白核心和一个氨基末端，该末端对于家族中可能指定单个膜联蛋白特性的给定成员是唯一的。已经解决了几个高分辨率的晶体膜联蛋白结构(包括膜联蛋白I)；然而，已发表的膜联蛋白结构中没有一个包含完整的N-末端结构域。目前，我们已经能够表达、纯化和结晶全长人膜联蛋白I，通过解决全长人膜联蛋白I的结构，我们希望获得更多关于N-末端结构域如何与核心区相互作用的信息。此外，我们希望对膜联蛋白家族的这个成员如何参与膜相关的过程，包括膜聚集和融合，获得一些有用的见解。我们认为，在钙离子和磷酸根离子存在下，人膜联蛋白I的结构构象会发生改变。我们希望测试这种结构构象变化是否不仅通过解决天然全长人膜联蛋白I的结构发生，而且还通过在钙离子和磷酸根离子存在的情况下解决全长人膜联蛋白I的结构来发生。

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.