CRYSTAL STRUCTURES OF N-TERMINAL ECTODOMAINS OF CADHERIN-23

CADHERIN-23 N 端胞外域的晶体结构

• 批准号: 8361628
• 负责人: RACHELLE GAUDET
• 金额: $ 0.68万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361628
• 关键词: Adhesions; Architecture; Cadherins; Calcium ion; Elasticity; Funding; Grant; Hair Cells; Inherited; Labyrinth; Link; Mediating; Molecular; Mutation; N-terminal; National Center for Research Resources; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Source; Structure; United States National Institutes of Health; cost; deafness; human CDH23 protein; mutant; structural biology

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. The hair-cell tip link, an essential component of the mechanotransduction apparatus in the inner ear, has been proposed to be formed partly by cadherin- 23 (CDH23) which is involved in hereditary deafness and belongs to the cadherin superfamily of proteins. Calcium ions are required for cadherin- mediated adhesion and also for maintaining the integrity of the tip link. Hair cells have an elastic gating spring, but it is unclear whether tip links have the appropriate elasticity. Certain mutations in CDH23 cause deafness, but it is not known how. In order to investigate the molecular architecture and elasticity of the tip link and its deafness related mutants we determined the x-ray crystallographic structures of key CDH23 domains involved on tip link assembly and deafness.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 毛细胞尖端连接是内耳机械传导装置的重要组成部分，已被认为部分由钙粘蛋白-23 (CDH23) 形成，钙粘蛋白与遗传性耳聋有关，属于钙粘蛋白超家族。钙粘蛋白介导的粘附以及维持尖端连接的完整性都需要钙离子。毛细胞具有弹性门控弹簧，但尚不清楚尖端链接是否具有适当的弹性。 CDH23 的某些突变会导致耳聋，但具体机制尚不清楚。为了研究尖端链接及其耳聋相关突变体的分子结构和弹性，我们确定了涉及尖端链接组装和耳聋的关键 CDH23 结构域的 X 射线晶体结构。