4p9l | pdb_00004p9l

Crystal Structure of mouse Ryanodine Receptor 2 SPRY2 Domain (1080-1253) disease mutant A1107M

spinqualitylabelsall models 4p9l, resolution 1.44Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p9l is a 1 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 1.4361Å 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ryanodine receptor 3D structures

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