4ETU

Crystal structure of rabbit ryanodine receptor 1 mutant R2939S

Summary for 4ETU

• Entry DOI: 10.2210/pdb4etu/pdb
• Related: 4ERT 4ERV 4ESU 4ETT 4ETV
• Descriptor: Ryanodine receptor 1, GLYCEROL (3 entities in total)
• Functional Keywords: ryanodine receptor calcium release channel, phosphorylation, muscle, skeletal, metal transport
• Biological source: Oryctolagus cuniculus (rabbit)
• Cellular location: Sarcoplasmic reticulum membrane ; Multi-pass membrane protein : P11716
• Total number of polymer chains: 1
• Total formula weight: 24867.92

Authors

Yuchi, Z.,Lau, K.,Van Petegem, F. (deposition date: 2012-04-24, release date: 2012-06-13, Last modification date: 2023-09-13)

Primary citation

Yuchi, Z.,Lau, K.,Van Petegem, F.
Disease mutations in the ryanodine receptor central region: crystal structures of a phosphorylation hot spot domain.
Structure, 20:1201-1211, 2012

PubMed Abstract: Ryanodine Receptors (RyRs) are huge Ca²⁺ 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.

PubMed: 22705209
DOI: 10.1016/j.str.2012.04.015

Experimental method

X-RAY DIFFRACTION (2.19 Å)