CRYSTALLOGRAPHIC STUDIES OF C2 DOMAINS

C2 域的晶体学研究

• 批准号: 8362288
• 负责人: ROGER BRYAN SUTTON
• 金额: $ 0.41万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362288
• 关键词: Affinity; Binding; C2 Domain; Calcium ion; DYSF gene; Data; Disease; Etiology; Funding; Grant; Human; Limb-Girdle Muscular Dystrophies; Mutation; N-terminal; National Center for Research Resources; Phospholipids; Principal Investigator; Process; Protein Array; Proteins; Radiation; Regulation; Research; Research Infrastructure; Resources; Source; Structure; United States National Institutes of Health; Work; cost; structural biology; synaptotagmin I; three dimensional structure; ultra high resolution

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. C2 domains are common phospholipid binding motifs used by an array of proteins. My lab has successfully crystallized C2 domains from a variety of proteins, and we have solved the structures of some these domains using ultra high resolution diffraction data collected at SSRL. While the fold of these domains is well known, the regulation of C2 domains and their involvement in disease processes are still not understood. Here, we will investigate two proteins that utilize C2 domains to answer the aforementioned questions. The first is a continuation of our previous work with the C2 domains of synaptotagmin 1. Our hypothesis is that the ?un-structured linker? domain, which is N-terminal to the main body of the C2 domain, can interact with the Ca+2 binding pocket of C2A to modify the affinity for calcium ion. The second project involves determining the 3D structure of the 7 C2 domains of human dysferlin. Mutations within these C2 domains are known to cause Limb-Girdle muscular dystrophy in humans, and structural information is essential to understand the etiology of this disease.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 C2结构域是一系列蛋白质使用的常见磷脂结合基序。 我的实验室已经成功地从各种蛋白质中结晶出C2结构域，并且我们已经使用SSRL收集的超高分辨率衍射数据解决了其中一些结构域的结构。虽然这些结构域的折叠是众所周知的，但C2结构域的调节及其在疾病过程中的参与仍然不清楚。在这里，我们将研究两种利用C2结构域来回答上述问题的蛋白质。第一个是我们以前的工作与突触结合蛋白1的C2域的延续。 我们的假设是？非结构化连接器？C2结构域的N-末端可以与C2 A的Ca+2结合口袋相互作用以改变对钙离子的亲和力。 第二个项目涉及确定人dysferlin的7个C2结构域的3D结构。 已知这些C2结构域内的突变会导致人类的肢带型肌营养不良症，并且结构信息对于理解这种疾病的病因至关重要。