4ETU: Crystal structure of rabbit ryanodine receptor 1 mutant R2939S

Ryanodine Receptors (RyRs) are huge Ca(2)(+) release channels in the endoplasmic reticulum membrane and form targets for phosphorylation and disease mutations. We present crystal structures of a domain in three RyR isoforms, containing the Ser2843 (RyR1) and Ser2808/Ser2814 (RyR2) phosphorylation sites. The RyR1 domain is the target for 11 disease mutations. Several of these are clustered near the phosphorylation sites, suggesting that phosphorylation and disease mutations may affect the same interface. The L2867G mutation causes a drastic thermal destabilization and aggregation at room temperature. Crystal structures for other disease mutants show that they affect surface properties and intradomain salt bridges. In vitro phosphorylation experiments show that up to five residues in one long loop of RyR2 can be phosphorylated by PKA or CaMKII. Docking into cryo-electron microscopy maps suggests a putative location in the clamp region, implying that mutations and phosphorylation may affect the allosteric motions within this area.
PDB ID: 4ETUDownload
MMDB ID: 100576
PDB Deposition Date: 2012/4/24
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.19  Å
Source Organism:
Similar Structures:
Biological Unit for 4ETU: monomeric; determined by author and by software (PISA)
Molecular Components in 4ETU
Label Count Molecule
Protein (1 molecule)
Ryanodine Receptor 1(Gene symbol: RYR1)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB