7tdi

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Rabbit RyR1 with AMP-PCP and high Ca2+ embedded in nanodisc in closed-inactivated conformation class 2 (Dataset-A)

Structural highlights

7tdi is a 4 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:ACP, CA, ZN
NonStd Res:UNK
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RYR1_RABIT] Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).[1] [2]

Publication Abstract from PubMed

Activation of the intracellular Ca(2+) channel ryanodine receptor (RyR) triggers a cytosolic Ca(2+) surge, while elevated cytosolic Ca(2+) inhibits the channel in a negative feedback mechanism. Cryo-EM of rabbit RyR1 embedded in nanodiscs under partially inactivating Ca(2+) conditions revealed an open and a closed-inactivated conformation. Ca(2+) binding to the high affinity site engages the central and C-terminal domains into a block, which pries the S6 four-helix bundle open. Further rotation of this block pushes S6 toward the central axis, closing (inactivating) the channel. Main characteristics of the Ca(2+)-inactivated conformation are downward conformation of the cytoplasmic assembly and tightly-knit subunit interface contributed by a fully occupied Ca(2+) activation site, two inter-subunit resolved lipids, and two salt bridges between the EF hand domain and the S2-S3 loop validated by disease-causing mutations. The structural insight illustrates the prior Ca(2+) activation prerequisite for Ca(2+) inactivation and provides for seamless transition from inactivated to closed conformations.

Ca(2+)-inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM.,Nayak AR, Samso M Elife. 2022 Mar 8;11. pii: 75568. doi: 10.7554/eLife.75568. PMID:35257661[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
1 reviews cite this structure
Three-dimensional perspective on ryanodine receptor mutations causing skeletal and cardiac muscle-related diseases.
Iyer et al. (2023)
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8 other articles
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See Also

References

  1. ↑ Dulhunty AF, Laver DR, Gallant EM, Casarotto MG, Pace SM, Curtis S. Activation and inhibition of skeletal RyR channels by a part of the skeletal DHPR II-III loop: effects of DHPR Ser687 and FKBP12. Biophys J. 1999 Jul;77(1):189-203. PMID:10388749 doi:10.1016/S0006-3495(99)76881-5
  2. ↑ Kakizawa S, Yamazawa T, Chen Y, Ito A, Murayama T, Oyamada H, Kurebayashi N, Sato O, Watanabe M, Mori N, Oguchi K, Sakurai T, Takeshima H, Saito N, Iino M. Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function. EMBO J. 2011 Oct 28;31(2):417-28. doi: 10.1038/emboj.2011.386. PMID:22036948 doi:10.1038/emboj.2011.386
  3. ↑ Nayak AR, Samso M. Ca(2+)-inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM. Elife. 2022 Mar 8;11. pii: 75568. doi: 10.7554/eLife.75568. PMID:35257661 doi:http://dx.doi.org/10.7554/eLife.75568

Contents


PDB ID 7tdi

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OCA

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