RYANODINE RECEPTOR FROM RABBIT SKELETAL MUSCLE

该子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心赠款提供。次级项目的主要支助 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。 为子项目列出的总成本可能 表示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。 Ca 2+释放通道（也称为ryanodine受体，RyR）属于一个家族， 膜钙离子通道是目前已知的最大的离子通道。在哺乳动物中， 存在三种同源RyR同种型。它们70%的序列同源性解释了 它们之间有许多功能相似之处。RyR 1主要存在于骨骼肌中， 介导Ca 2+从肌浆网（SR）库释放到细胞质中 在收缩期间。RyR 1由于其在SR中的高浓度而被研究得最多 膜及其相对简单的纯化。该通道由四个子单元组成， 每个约565 kDa，构成了一个单一的同源四聚体阳离子选择性通道孔中， SR膜。该通道的突变与几种人类肌肉相关。 遗传性疾病，如恶性高热（MH）和称为中央核心的肌病 疾病（CCD）。 我们正在使用单粒子cryoEM来确定其最高可能分辨率的结构， 不同的生理状态和cryoEM约束建模，以确定不同的 域.

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 Ca2+ release channel (also known as the ryanodine receptor, RyR) belongs to a family of integral membrane Ca2+ channels and is the largest known ion channel. In mammals, there are three homologous RyR isoforms. Their 70% sequence homology accounts for the many functional similarities between them. RyR1 is found primarily in skeletal muscle and mediates the release of Ca2+ from sarcoplasmic reticulum (SR) stores into the cytoplasm during contraction. RyR1 is the most studied due to its high concentration in the SR membrane and its relatively simple purification. The channel is composed of four subunits, each ~565 kDa, constituting a single homotetrameric cation-selective channel pore in the SR membrane. Mutations in this channel are associated with several human muscular genetic diseases such as malignant hyperthermia (MH) and the myopathy called central core disease (CCD). We are using single particle cryoEM to determine its highest possible resolution structure at different physiological states and cryoEM restrained modeling to determine folds of different domains.