STUDIES OF THE INTERACTION OF ANNEXIN V, CALCIUM, ZINC AND PHOSPHOLIPIDS USING

使用Annexin V、钙、锌和磷脂相互作用的研究

• 批准号: 7601393
• 负责人: BRIAN GENGE
• 金额: $ 0.03万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601393
• 关键词: Annexins; Binding; Binding Proteins; Biological; Calcium; Cartilage; Chondrocytes; Computer Retrieval of Information on Scientific Projects Database; Electrolytes; Epiphysial cartilage; Event; Funding; Grant; Institution; Ions; Ligands; Membrane Proteins; Osteoarthrosis Deformans; Phosphatidylserines; Phospholipids; Play; Positioning Attribute; Proteins; Research; Research Personnel; Resources; Role; Running; Source; Structure; Thinking; Tissues; Tryptophan; United States National Institutes of Health; Vesicle; Zinc; annexin A5; biomineralization; insight; mineralization; simulation

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. Matrix vesicles are chondrocyte-derived microstructures found in a variety of mineralizing tissues such as growth plate and osteoarthritic cartilage. Matrix vesicles contain significant amounts of phospholipids, electrolytes and Annexin V protein. Annexin V is a calcium / zinc phospholipid-dependent binding protein that is thought to play a key role in the initiation of biomineralization. We have obtained crystal structures of Annexin V in the presence of calcium and zinc ions. However, no crystal structures showing the position of the proteins ligand, phosphatidylserine, are yet available. It is known however, that Annexin V undergoes a conformational change upon calcium-dependent acidic phospholipid binding, where a single tryptophan residue moves from a hydrophobic region within the protein to an extended position on the outer protein surface. Accordingly, I am requesting the use of Teragrid computational resources to run NAMD simulations on Annexin V, in the presence / absence of calcium, zinc, and various phospholipids and phospholipids bilayers. These studies could provide insight into the initial events involved in the mechanism of biological mineralization.

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。 基质囊泡是软骨细胞衍生的微观结构，存在于各种矿化组织如生长板和骨关节炎软骨中。基质囊泡含有大量的磷脂、电解质和膜联蛋白V蛋白。膜联蛋白V是一种钙/锌磷脂依赖性结合蛋白，被认为在生物矿化的启动中起关键作用。我们已经获得了钙和锌离子存在下的膜联蛋白V的晶体结构。然而，没有晶体结构显示的位置的蛋白质配体，磷脂酰丝氨酸，尚未获得。然而，已知膜联蛋白V在钙依赖性酸性磷脂结合后经历构象变化，其中单个色氨酸残基从蛋白质内的疏水区域移动到蛋白质外表面上的延伸位置。因此，我请求使用Teragrid计算资源，在钙、锌和各种磷脂和磷脂双层存在/不存在的情况下，对膜联蛋白V进行NAMD模拟。这些研究可以为生物矿化机制中涉及的初始事件提供深入了解。