3RQR

Crystal structure of the RYR domain of the rabbit ryanodine receptor

Summary for 3RQR

• Entry DOI: 10.2210/pdb3rqr/pdb
• Descriptor: Ryanodine receptor 1, (UNK)(UNK)(UNK)(UNK) (3 entities in total)
• Functional Keywords: ryanodine receptor, ryr domain, metal transport
• Biological source: Oryctolagus cuniculus (rabbit); More
• Cellular location: Sarcoplasmic reticulum membrane; Multi-pass membrane protein: P11716
• Total number of polymer chains: 2
• Total formula weight: 26838.20

Authors

Nair, U.B.,Li, W.,Dong, A.,Walker, J.R.,Gramolini, A.,Bountra, C.,Weigelt, J.,Arrowsmith, C.H.,Edwards, A.M.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (deposition date: 2011-04-28, release date: 2011-06-22, Last modification date: 2024-02-28)

Primary citation

Sharma, P.,Ishiyama, N.,Nair, U.,Li, W.,Dong, A.,Miyake, T.,Wilson, A.,Ryan, T.,Maclennan, D.H.,Kislinger, T.,Ikura, M.,Dhe-Paganon, S.,Gramolini, A.O.
Structural determination of the phosphorylation domain of the ryanodine receptor.
Febs J., 279:3952-3964, 2012

PubMed Abstract: The ryanodine receptor (RyR) is a large, homotetrameric sarcoplasmic reticulum membrane protein that is essential for Ca(2+) cycling in both skeletal and cardiac muscle. Genetic mutations in RyR1 are associated with severe conditions including malignant hyperthermia (MH) and central core disease. One phosphorylation site (Ser 2843) has been identified in a segment of RyR1 flanked by two RyR motifs, which are found exclusively in all RyR isoforms as closely associated tandem (or paired) motifs, and are named after the protein itself. These motifs also contain six known MH mutations. In this study, we designed, expressed and purified the tandem RyR motifs, and show that this domain contains a putative binding site for the Ca(2+)/calmodulin-dependent protein kinase β isoform. We present a 2.2 Å resolution crystal structure of the RyR domain revealing a two-fold, symmetric, extended four-helix bundle stabilized by a β sheet. Using mathematical modelling, we fit our crystal structure within a tetrameric electron microscopy (EM) structure of native RyR1, and propose that this domain is localized in the RyR clamp region, which is absent in its cousin protein inositol 1,4,5-trisphosphate receptor.

PubMed: 22913516
DOI: 10.1111/j.1742-4658.2012.08755.x

Experimental method

X-RAY DIFFRACTION (2.16 Å)