5c33

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Crystal Structure of Mouse Ryanodine Receptor 2 SPRY1 Domain

Structural highlights

5c33 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.21Å
Ligands:CL, CME, IPA
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RYR2_MOUSE Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering cardiac muscle contraction. Aberrant channel activation can lead to cardiac arrhythmia. In cardiac myocytes, calcium release is triggered by increased Ca(2+) levels due to activation of the L-type calcium channel CACNA1C. The calcium channel activity is modulated by formation of heterotetramers with RYR3. Required for cellular calcium ion homeostasis. Required for embryonic heart development.[1] [2] [3] [4]

Publication Abstract from PubMed

Ryanodine receptors (RyRs) form calcium release channels located in the membranes of the sarcoplasmic and endoplasmic reticulum. RyRs play a major role in excitation-contraction coupling and other Ca(2+)-dependent signalling events, and consist of several globular domains that together form a large assembly. Here we describe the crystal structures of the SPRY1 and tandem-repeat domains at 1.2-1.5 A resolution, which reveal several structural elements not detected in recent cryo-EM reconstructions of RyRs. The cryo-EM studies disagree on the position of SPRY domains, which had been proposed based on homology modelling. Computational docking of the crystal structures, combined with FRET studies, show that the SPRY1 domain is located next to FK506-binding protein (FKBP). Molecular dynamics flexible fitting and mutagenesis experiments suggest a hydrophobic cluster within SPRY1 that is crucial for FKBP binding. A RyR1 disease mutation, N760D, appears to directly impact FKBP binding through interfering with SPRY1 folding.

Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant.,Yuchi Z, Yuen SM, Lau K, Underhill AQ, Cornea RL, Fessenden JD, Van Petegem F Nat Commun. 2015 Aug 6;6:7947. doi: 10.1038/ncomms8947. PMID:26245150[5]

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

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See Also

References

  1. ↑ Zhao M, Li P, Li X, Zhang L, Winkfein RJ, Chen SR. Molecular identification of the ryanodine receptor pore-forming segment. J Biol Chem. 1999 Sep 10;274(37):25971-4. PMID:10473538
  2. ↑ Takeshima H, Komazaki S, Hirose K, Nishi M, Noda T, Iino M. Embryonic lethality and abnormal cardiac myocytes in mice lacking ryanodine receptor type 2. EMBO J. 1998 Jun 15;17(12):3309-16. PMID:9628868 doi:10.1093/emboj/17.12.3309
  3. ↑ van Oort RJ, McCauley MD, Dixit SS, Pereira L, Yang Y, Respress JL, Wang Q, De Almeida AC, Skapura DG, Anderson ME, Bers DM, Wehrens XH. Ryanodine receptor phosphorylation by calcium/calmodulin-dependent protein kinase II promotes life-threatening ventricular arrhythmias in mice with heart failure. Circulation. 2010 Dec 21;122(25):2669-79. doi: 10.1161/CIRCULATIONAHA.110.982298., Epub 2010 Nov 15. PMID:21098440 doi:10.1161/CIRCULATIONAHA.110.982298
  4. ↑ Guo T, Cornea RL, Huke S, Camors E, Yang Y, Picht E, Fruen BR, Bers DM. Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks. Circ Res. 2010 Jun 11;106(11):1743-52. doi: 10.1161/CIRCRESAHA.110.219816. Epub, 2010 Apr 29. PMID:20431056 doi:10.1161/CIRCRESAHA.110.219816
  5. ↑ Yuchi Z, Yuen SM, Lau K, Underhill AQ, Cornea RL, Fessenden JD, Van Petegem F. Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant. Nat Commun. 2015 Aug 6;6:7947. doi: 10.1038/ncomms8947. PMID:26245150 doi:http://dx.doi.org/10.1038/ncomms8947

Contents


PDB ID 5c33

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