4P9L
Crystal Structure of mouse Ryanodine Receptor 2 SPRY2 Domain (1080-1253) disease mutant A1107M
Summary for 4P9L
| Entry DOI | 10.2210/pdb4p9l/pdb |
| Related | 4PNI |
| Descriptor | Ryanodine receptor 2 (2 entities in total) |
| Functional Keywords | ion channel, calcium, signalling, metal transport, transport protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 19954.37 |
| Authors | Lau, K.,Van Petegem, F. (deposition date: 2014-04-04, release date: 2014-11-05, Last modification date: 2023-12-27) |
| Primary citation | Lau, K.,Van Petegem, F. Crystal structures of wild type and disease mutant forms of the ryanodine receptor SPRY2 domain. Nat Commun, 5:5397-5397, 2014 Cited by PubMed Abstract: 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 Å resolution. They form two antiparallel β 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. PubMed: 25370123DOI: 10.1038/ncomms6397 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4361 Å) |
Structure validation
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