4P9I: Crystal Structure of mouse Ryanodine Receptor 2 SPRY2 Domain (1080-1253)

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.
PDB ID: 4P9IDownload
MMDB ID: 124475
PDB Deposition Date: 2014/4/4
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 1.3401  Å
Source Organism:
Similar Structures:
Biological Unit for 4P9I: monomeric; determined by author
Molecular Components in 4P9I
Label Count Molecule
Protein (1 molecule)
Ryanodine Receptor 2(Gene symbol: Ryr2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB