RYANODINE RECEPTOR FROM RABBIT SKELETAL MUSCLE

来自兔骨骼肌的兰尼碱受体

• 批准号: 7953759
• 负责人: SUSAN L HAMILTON
• 金额: $ 3.48万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953759
• 关键词: Accounting; Cations; Central Core Myopathy; Computer Retrieval of Information on Scientific Projects Database; Cryoelectron Microscopy; Cytoplasm; Electron Microscopy; Family; Funding; Grant; Hereditary Disease; Human; Institution; Ion Channel; Malignant hyperpyrexia due to anesthesia; Mammals; Mediating; Membrane; Modeling; Muscle; Mutation; Myopathy; Oryctolagus cuniculus; Physiological; Protein Isoforms; Research; Research Personnel; Resolution; Resources; RyR1; Ryanodine Receptor Calcium Release Channel; Ryanodine Receptors; Sarcoplasmic Reticulum; Sequence Homology; Skeletal Muscle; Source; Structure; United States National Institutes of Health; macromolecule; particle

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 Ca2+ 释放通道（也称为兰尼碱受体，RyR）属于整合膜 Ca2+ 通道家族，是已知最大的离子通道。在哺乳动物中，存在三种同源的 RyR 同工型。它们 70% 的序列同源性解释了它们之间的许多功能相似性。 RyR1 主要存在于骨骼肌中，在收缩过程中介导 Ca2+ 从肌浆网 (SR) 储存释放到细胞质中。 RyR1 由于在 SR 膜中的浓度较高且纯化相对简单，因此研究最多。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。该通道的突变与多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（CC​​D）的肌病。 我们使用单粒子冷冻电镜来确定其在不同生理状态下的最高分辨率结构，并使用冷冻电镜约束建模来确定不同域的折叠。