RYANODINE RECEPTOR FROM RABBIT SKELETAL MUSCLE

来自兔骨骼肌的兰尼碱受体

• 批准号: 8361061
• 负责人: SUSAN L HAMILTON
• 金额: $ 1.23万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361061
• 关键词: Accounting; Cations; Central Core Myopathy; Cryoelectron Microscopy; Cytoplasm; Electron Microscopy; Family; Funding; Grant; Hereditary Disease; Human; Ion Channel; Malignant hyperpyrexia due to anesthesia; Mammals; Mediating; Membrane; Modeling; Muscle; Mutation; Myopathy; National Center for Research Resources; Oryctolagus cuniculus; Physiological; Principal Investigator; Protein Isoforms; Research; Research Infrastructure; Resolution; Resources; RyR1; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Sequence Homology; Skeletal Muscle; Source; Structure; United States National Institutes of Health; cost; macromolecule; particle

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且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。 子项目可能列出的总成本 代表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。 Ca2+ 释放通道（也称为兰尼碱受体，RyR）属于一个家族 膜内 Ca2+ 通道的组成，是已知最大的离子通道。在哺乳动物中， 存在三种同源的 RyR 亚型。它们 70% 的序列同源性 它们之间有许多功能相似之处。 RyR1 主要存在于骨骼肌中 介导 Ca2+ 从肌浆网 (SR) 储存释放到细胞质中 收缩期间。 RyR1 由于其在 SR 中的浓度较高而被研究得最多 膜及其纯化相对简单。该通道由四个子单元组成， 每个〜565 kDa，构成单个同源四聚体阳离子选择性通道孔 SR膜。该通道的突变与多种人类肌肉相关 遗传性疾病，例如恶性高热 (MH) 和称为中央核心的肌病 疾病（CC​​D）。 我们正在使用单粒子冷冻电镜来确定其最高分辨率的结构 不同的生理状态和冷冻电镜约束建模以确定不同的褶皱 域。