CRYSTAL STRUCTURES OF ONE AND TWO N-TERMINAL ECTODOMAINS OF CADHERIN-23

该子项目是利用 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，不一定是研究者的机构。 毛细胞顶端连接是内耳机械传导装置的重要组成部分，已被提出部分由钙粘蛋白23（CDH 23）形成，钙粘蛋白23参与遗传性耳聋并且属于钙粘蛋白超家族蛋白质。钙离子是钙粘蛋白介导的粘附所必需的，也是维持头端连接完整性所必需的。毛细胞具有弹性门控弹簧，但不清楚尖端链接是否具有适当的弹性。CDH 23中的某些突变会导致耳聋，但不知道是如何引起的。为了研究尖端连接及其耳聋相关突变体的分子结构和弹性，我们的目标是确定参与尖端连接组装和耳聋的关键CDH 23结构域的X射线晶体学结构。

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. 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 aim to determine the x-ray crystallographic structures of key CDH23 domains involved on tip link assembly and deafness.