4p9j

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Crystal Structure of rabbit Ryanodine Receptor 1 SPRY2 Domain (1070-1246)

Structural highlights

4p9j is a 3 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.84Å
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

Ryanodine receptors (RyRs) form channels responsible for the release of Ca(2+) from the endoplasmic and sarcoplasmic reticulum. The SPRY2 domain in the skeletal muscle isoform (RyR1) has been proposed as a direct link with L-type calcium channels (CaV1.1), allowing for direct mechanical coupling between plasma membrane depolarization and Ca(2+) release. Here we present the crystal structures of the SPRY2 domain from RyR1 and RyR2 at 1.34-1.84 A resolution. They form two antiparallel beta sheets establishing a core, and four additional modules of which several are required for proper folding. A buried disease mutation, linked to hypertrophic cardiomyopathy and loss-of-function, induces local misfolding and strong destabilization. Isothermal titration calorimetry experiments negate the RyR1 SPRY2 domain as the major link with CaV1.1. Instead, docking into full-length RyR1 cryo-electron microscopy maps suggests that the SPRY2 domain forms a link between the N-terminal gating ring and the clamp region.

Crystal structures of wild type and disease mutant forms of the ryanodine receptor SPRY2 domain.,Lau K, Van Petegem F Nat Commun. 2014 Nov 5;5:5397. doi: 10.1038/ncomms6397. PMID:25370123[3]

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

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Citations
10 reviews cite this structure
Ryanodine Receptor Structure and Function in Health and Disease.
Santulli et al. (2018)
9 more
24 other articles
No citations found

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. ↑ Lau K, Van Petegem F. Crystal structures of wild type and disease mutant forms of the ryanodine receptor SPRY2 domain. Nat Commun. 2014 Nov 5;5:5397. doi: 10.1038/ncomms6397. PMID:25370123 doi:http://dx.doi.org/10.1038/ncomms6397

Contents


PDB ID 4p9j

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OCA

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