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

这个子项目是许多利用 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所在的机构。 膜联蛋白是以钙依赖性方式与带负电荷的磷脂结合的可溶性蛋白质。 膜联蛋白家族的每个成员包括两个主要结构域：保守的羧基末端蛋白质核心和氨基末端，该氨基末端对于该家族的给定成员是独特的，其可以指定个体膜联蛋白性质。 一些高分辨率的晶体膜联蛋白结构已被解决（包括膜联蛋白I），但是，没有一个公布的膜联蛋白结构包含一个完整的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。 通过解析全长人膜联蛋白I的结构，我们希望获得更多关于N端结构域如何与核心结构域相互作用的信息。 此外，我们希望获得一些有用的见解，这个成员的膜联蛋白家族是如何牵连在膜相关的过程，包括膜聚集和融合。 我们建议，在钙离子和磷酸根离子的存在下，人膜联蛋白I的结构构象将被改变。 我们希望通过不仅解析天然全长人膜联蛋白I的结构，而且在钙和磷酸根离子存在下解析全长人膜联蛋白I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.