3rqr

Publication Abstract from PubMed

The ryanodine receptor (RyR) is a large, homotetrameric sarcoplasmic reticulum (SR) membrane protein 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 (CCD). 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 organized as closely-associated tandem (or paired) motifs, and 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 beta isoform. We present a 2.2A resolution crystal structure of the RyR domain revealing a two-fold, symmetric, extended four-helix bundle stabilized by a beta-sheet. Using mathematical modelling we fit our crystal structure within a tetrameric EM structure of native RyR1 and propose that this domain is localized in the RyR's clamp region, which is absent in its cousin protein inositol 1,4,5-trisphosphate receptor. (c) 2012 The Authors Journal compilation (c) 2012 FEBS.

Structural Determination of the Phosphorylation Domain of the Ryanodine Receptor.,Sharma P, Ishiyama N, Nair U, Li W, Dong A, Miyake T, Wilson A, Ryan T, Maclennan DH, Kislinger T, Ikura M, Dhe-Paganon S, Gramolini AO FEBS J. 2012 Aug 22. doi: 10.1111/j.1742-4658.2012.08755.x. PMID:22913516^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.