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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 毛细胞顶端连接是内耳机械转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，CDH23与遗传性耳聋有关，属于钙粘蛋白超家族蛋白。钙离子是钙粘附素介导的黏附所必需的，也是维持尖端连接完整性所必需的。毛细胞有一个弹性的闸门弹簧，但尚不清楚尖端的连接是否具有适当的弹性。CDH23的某些突变会导致耳聋，但具体原因尚不清楚。为了研究TIP链及其耳聋相关突变体的分子结构和弹性，我们的目标是确定与TIP链组装和耳聋相关的关键CDH23结构域的X射线晶体结构。

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.