RYANODINE RECEPTOR FROM RABBIT SKELETAL MUSCLE

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。子项目和 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。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 Ca 2+释放通道（也称为ryanodine受体，RyR）属于完整膜Ca 2+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同种型。它们70%的序列同源性解释了它们之间的许多功能相似性。RyR 1主要存在于骨骼肌中，并在收缩期间介导Ca 2+从肌浆网（SR）储存释放到细胞质中。RyR 1由于其在SR膜中的高浓度和其相对简单的纯化而被研究得最多。该通道由四个亚基组成，每个亚基约565 kDa，构成SR膜中的单个同源四聚体阳离子选择性通道孔。该通道中的突变与几种人类肌肉遗传疾病有关，例如恶性高热（MH）和称为中央核心疾病（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的最高可能分辨率结构，并使用cryoEM约束建模来确定不同域的折叠。

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.