RYANODINE RECEPTOR FROM RABBIT SKELETAL MUSCLE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。钙释放通道(又称Ryanodine受体，RyR)属于完整的膜钙通道家族，是已知最大的离子通道。在哺乳动物中，有三种同源的RyR亚型。它们70%的序列同源性解释了它们之间许多功能上的相似性。RyR1主要存在于骨骼肌中，在收缩过程中介导肌浆网(SR)储存的钙离子释放到细胞质中。研究最多的是RyR1，因为它在SR膜中的浓度很高，而且纯化相对简单。该通道由四个亚基组成，每个亚基约565 kDa，在SR膜上构成一个单一的同源四聚体阳离子选择性通道孔。这一通道中的突变与几种人类肌肉遗传病有关，如恶性高热(MH)和称为中枢性核心病(CCD)的肌病。我们正在使用单粒子CryoEM来确定其在不同生理状态下可能的最高分辨率结构，并使用CryoEM约束建模来确定不同结构域的折叠。

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 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.