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-Structure paper
Title | The Central domain of RyR1 is the transducer for long-range allosteric gating of channel opening. |
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Journal, issue, pages | Cell Res, Vol. 26, Issue 9, Page 995-991006, Year 2016 |
Publish date | Jul 29, 2016 |
Authors | Xiao-Chen Bai / Zhen Yan / Jianping Wu / Zhangqiang Li / Nieng Yan / |
PubMed Abstract | The ryanodine receptors (RyRs) are intracellular calcium channels responsible for rapid release of Ca(2+) from the sarcoplasmic/endoplasmic reticulum (SR/ER) to the cytoplasm, which is essential for ...The ryanodine receptors (RyRs) are intracellular calcium channels responsible for rapid release of Ca(2+) from the sarcoplasmic/endoplasmic reticulum (SR/ER) to the cytoplasm, which is essential for the excitation-contraction (E-C) coupling of cardiac and skeletal muscles. The near-atomic resolution structure of closed RyR1 revealed the molecular details of this colossal channel, while the long-range allosteric gating mechanism awaits elucidation. Here, we report the cryo-EM structures of rabbit RyR1 in three closed conformations at about 4 Å resolution and an open state at 5.7 Å. Comparison of the closed RyR1 structures shows a breathing motion of the cytoplasmic platform, while the channel domain and its contiguous Central domain remain nearly unchanged. Comparison of the open and closed structures shows a dilation of the S6 tetrahelical bundle at the cytoplasmic gate that leads to channel opening. During the pore opening, the cytoplasmic "O-ring" motif of the channel domain and the U-motif of the Central domain exhibit coupled motion, while the Central domain undergoes domain-wise displacement. These structural analyses provide important insight into the E-C coupling in skeletal muscles and identify the Central domain as the transducer that couples the conformational changes of the cytoplasmic platform to the gating of the central pore. |
External links | Cell Res / PubMed:27468892 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.8 - 5.7 Å |
Structure data | EMDB-9518: Cryo-EM map of RyR1 in a closed state (C1 conformer) EMDB-9519: Cryo-EM map of RyR1 in a closed state (C3 conformer) |
Chemicals | ChemComp-ZN: |
Source |
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Keywords | TRANSPORT PROTEIN/ISOMERASE / channel / membrane protein / TRANSPORT PROTEIN-ISOMERASE complex |