RABBIT SKELETAL RYANODINE RECEPTOR CRYSTAL STRUCTURE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们的总体目标是发展一个原子水平的理解钙释放从细胞内存储通过钙（Ca 2+）释放通道/ryanodine受体（RyRs），这是所需的兴奋收缩（EC）耦合骨骼肌和心肌。我们的目的是阐明骨骼（RyR 1）钙释放通道的结构与功能的关系。在过去的几年中，在确定通道的功能结构域和理解FK 506结合蛋白（FKBP也称为钙稳定蛋白）在调节RyR功能方面取得了重要进展。该提案的目的是将这些观察扩展到原子水平分辨率，并扩大我们对钙蛋白调节RyRs通道功能及其在人类疾病中的作用和作为药物靶标的机制的理解。

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.