Ca²⁺-release channels are giant membrane proteins that control the release of Ca²⁺ from the endoplasmic and sarcoplasmic reticulum. The two members, ryanodine receptors (RyRs) and inositol-1,4,5-trisphosphate Receptors (IP₃Rs), are evolutionarily related and are both activated by cytosolic Ca²⁺. They share a common architecture, but RyRs have evolved additional modules in the cytosolic region. Their massive size allows for the regulation by tens of proteins and small molecules, which can affect the opening and closing of the channels. In addition to Ca²⁺, other major triggers include IP₃ for the IP₃Rs, and depolarization of the plasma membrane for a particular RyR subtype. Their size has made them popular targets for study via electron microscopic methods, with current structures culminating near 3Å. The available structures have provided many new mechanistic insights int the binding of auxiliary proteins and small molecules, how these can regulate channel opening, and the mechanisms of disease-associated mutations. They also help scrutinize previously proposed binding sites, as some of these are now incompatible with the structures. Many questions remain around the structural effects of post-translational modifications, additional binding partners, and the higher-order complexes these channels can make in situ. This review summarizes our current knowledge about the structures of Ca²⁺-release channels and how this informs on their function.

中文翻译：

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钙释放通道：IP3 受体和 Ryanodine 受体的结构和功能

Ca ²⁺释放通道是巨大的膜蛋白，可控制内质网和肌质网释放 Ca ²⁺。这两个成员，ryanodine 受体 (RyRs) 和肌醇-1,4,5-三磷酸受体 (IP ₃ Rs)，在进化上相关并且都被胞质 Ca ²⁺激活。它们共享一个共同的架构，但 RyRs 在细胞质区域进化出了额外的模块。它们的巨大尺寸允许由数十种蛋白质和小分子进行调节，这会影响通道的打开和关闭。除了 Ca ²⁺，其他主要触发因素包括 IP ₃的 IP ₃Rs 和特定 RyR 亚型的质膜去极化。它们的尺寸使它们成为通过电子显微镜方法进行研究的热门目标，目前的结构接近 3Å。可用的结构为辅助蛋白和小分子的结合、这些如何调节通道开放以及疾病相关突变的机制提供了许多新的机制见解。它们还有助于仔细检查以前提出的结合位点，因为其中一些现在与结构不兼容。许多问题仍然围绕着翻译后修饰的结构效应、额外的结合伙伴以及这些通道可以在原位产生的高阶复合物。这篇综述总结了我们目前对 Ca ²⁺结构的了解- 发布渠道以及这如何通知其功能。