RABBIT SKELETAL RYANODINE RECEPTOR CRYSTAL STRUCTURE

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。 我们的总体目标是在原子水平上了解骨骼肌和心肌中兴奋-收缩(EC)偶联所需的钙(Ca~(2+))释放通道/ryanodine受体(RyRs)的细胞内钙释放。我们的目标是阐明骨骼(RyR1)钙释放通道的结构-功能关系。在过去的几年里，在识别通道的功能结构域和了解FK506结合蛋白(FKBP，也称为calstain)在调节RyR功能中的作用方面取得了重要进展。这项建议的目的是将这些观察扩展到原子水平的分辨率，并扩大我们对Calstains调节RyRs通道功能的机制的理解，以及它在人类疾病中的作用和作为药物靶点的作用。

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. Our overall objective is to develop an atomic level understanding of the calcium release from intracellular stores via the calcium (Ca2+) release channels /ryanodine receptors (RyRs) which is required for excitation-contraction (EC) coupling in skeletal and cardiac muscle. We aim to elucidate structure-function relationships of the skeletal (RyR1) calcium release cannels. In the past few years, important advances have been achieved in terms of identifying functional domains of the channels and in understanding the role of the FK506 binding protein (FKBP also known as calstabin) in regulating RyR function. The aims of this proposal are designed to extend these observations to atomic level resolution and to expand our understanding of the mechanisms by which calstabins regulate RyRs channel function and its role in human diseases and as a drug target.