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 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.
Original language | English (US) |
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Pages (from-to) | 995-1006 |
Number of pages | 12 |
Journal | Cell Research |
Volume | 26 |
Issue number | 9 |
DOIs | |
State | Published - Sep 1 2016 |
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
Keywords
- RyR1
- calcium channel
- excitation-contraction coupling
- membrane transport
- voltage-gated calcium channels