Ryanodine receptor 1 (RyR1) mediates excitation-contraction coupling by releasing Ca2+ from sarcoplasmic reticulum (SR) to the cytoplasm of skeletal muscle cells. RyR1 activation is regulated by several proteins from both the cytoplasm and lumen of the SR. Here, we report the structure of RyR1 from native SR membranes in closed and open states. Compared to the previously reported structures of purified RyR1, our structure reveals helix-like densities traversing the bilayer approximately 5 nm from the RyR1 transmembrane domain and sarcoplasmic extensions linking RyR1 to a putative calsequestrin network. We document the primary conformation of RyR1 in situ and its structural variations. The activation of RyR1 is associated with changes in membrane curvature and movement in the sarcoplasmic extensions. Our results provide structural insight into the mechanism of RyR1 in its native environment.

中文翻译：

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天然膜中 RyR1 的结构。

Ryanodine 受体 1 (RyR1) 通过将 Ca2+ 从肌质网 (SR) 释放到骨骼肌细胞的细胞质来介导兴奋-收缩偶联。RyR1 的激活受来自 SR 细胞质和管腔的几种蛋白质的调节。在这里，我们报告了封闭和开放状态下天然 SR 膜的 RyR1 结构。与先前报道的纯化 RyR1 的结构相比，我们的结构揭示了从 RyR1 跨膜结构域穿过双层约 5 nm 的螺旋状密度，以及将 RyR1 连接到推定的 calsequestrin 网络的肌质延伸。我们在原位记录了 RyR1 的主要构象及其结构变化。RyR1 的激活与膜曲率的变化和肌浆延伸的运动有关。