STRUCTURAL ANALYSIS OF FULL-LENGTH ANNEXIN 1 AND 2 IN COMPLEX WITH SPECIFIC LIGA

全长膜联蛋白 1 和 2 与特定连接体复合物的结构分析

• 批准号: 7370376
• 负责人: ANJA A ROSENGARTH
• 金额: $ 0.24万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370376
• 关键词: STRUCTURAL; ANALYSIS; FULL; LENGTH; ANNEXIN

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 1 and 2 belong to a family of calcium- and phospholipid binding proteins of unknown function. They are structurally divided into a conserved core and a variable N-terminal domain. The core is responsible for calcium-dependent membrane binding, whereas the N-terminal domain regulates the specific function of each annexin. Annexins 1 and 2 are able to promote membrane aggregation in vitro, however the mechanism of this reaction is not known. In order to understand annexin-induced membrane aggregation, we solved the structure of full-length annexin 1 in the absence of calcium ions. This new structure indeed resulted in a hypothesis of annexin 1-induced membrane aggregation. We believe that the N-terminal domain might induce membrane aggregation after the protein is bound to a membrane in a calcium-dependent manner. Upon this binding event, the N-terminal domain that was buried in the core of the protein in the absence of calcium might become accessible and interact with a second membrane. In order to proof our hypothesis, we need to solve the structure of full-length annexin 1 in the presence of calcium. We already have crystals of annexin 1 in the presence of calcium and we would like to get higher resolution data. We also have crystals of annexin 2 in the presence and absence of calcium ions that we would like to investigate at your facility.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。膜联蛋白1和2属于功能未知的钙和磷脂结合蛋白家族。它们在结构上分为保守的核心和可变的N-末端结构域。核心负责钙依赖性膜结合，而N-末端结构域调节每个膜联蛋白的特定功能。膜联蛋白1和2能够促进体外膜聚集，然而该反应的机制尚不清楚。为了了解膜联蛋白诱导的膜聚集，我们解决了全长膜联蛋白1在钙离子的情况下的结构。这种新结构确实导致了膜联蛋白1诱导膜聚集的假设。我们认为，N-末端结构域可能诱导膜聚集后，蛋白质结合到膜上的钙依赖性的方式。在这种结合事件中，在没有钙的情况下埋藏在蛋白质核心中的N-末端结构域可能变得可接近并与第二层膜相互作用。为了证明我们的假设，我们需要解决钙存在下全长膜联蛋白1的结构。我们已经有了钙存在下的膜联蛋白1晶体，我们希望获得更高分辨率的数据。我们也有晶体的膜联蛋白2在存在和不存在钙离子，我们希望在您的设施进行调查。