3HSM

Crystal structure of distal N-terminal beta-trefoil domain of Ryanodine Receptor type 1

3HSM の概要

• エントリーDOI: 10.2210/pdb3hsm/pdb
• 分子名称: Ryanodine receptor 1 (2 entities in total)
• 機能のキーワード: beta-trefoil, calcium, calcium channel, calcium transport, glycoprotein, ion transport, ionic channel, membrane, phosphoprotein, receptor, s-nitrosylation, transmembrane, transport, signaling protein
• 由来する生物種: Oryctolagus cuniculus (rabbit)
• 細胞内の位置: Sarcoplasmic reticulum membrane ; Multi-pass membrane protein : P11716
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46550.46

構造登録者

Amador, F.J.,Liu, S.,Ishiyama, N.,Plevin, M.J.,Wilson, A.,MacLennan, D.H.,Ikura, M. (登録日: 2009-06-10, 公開日: 2009-07-28, 最終更新日: 2023-09-06)

主引用文献

Amador, F.J.,Liu, S.,Ishiyama, N.,Plevin, M.J.,Wilson, A.,MacLennan, D.H.,Ikura, M.
Crystal structure of type I ryanodine receptor amino-terminal beta-trefoil domain reveals a disease-associated mutation "hot spot" loop
Proc.Natl.Acad.Sci.USA, 106:11040-11044, 2009

PubMed Abstract: Muscle contraction and relaxation is regulated by transient elevations of myoplasmic Ca(2+). Ca(2+) is released from stores in the lumen of the sarco(endo)plasmic reticulum (SER) to initiate formation of the Ca(2+) transient by activation of a class of Ca(2+) release channels referred to as ryanodine receptors (RyRs) and is pumped back into the SER lumen by Ca(2+)-ATPases (SERCAs) to terminate the Ca(2+) transient. Mutations in the type 1 ryanodine receptor gene, RYR1, are associated with 2 skeletal muscle disorders, malignant hyperthermia (MH), and central core disease (CCD). The evaluation of proposed mechanisms by which RyR1 mutations cause MH and CCD is hindered by the lack of high-resolution structural information. Here, we report the crystal structure of the N-terminal 210 residues of RyR1 (RyR(NTD)) at 2.5 A. The RyR(NTD) structure is similar to that of the suppressor domain of type 1 inositol 1,4,5-trisphosphate receptor (IP(3)Rsup), but lacks most of the long helix-turn-helix segment of the "arm" domain in IP(3)Rsup. The N-terminal beta-trefoil fold, found in both RyR and IP(3)R, is likely to play a critical role in regulatory mechanisms in this channel family. A disease-associated mutation "hot spot" loop was identified between strands 8 and 9 in a highly basic region of RyR1. Biophysical studies showed that 3 MH-associated mutations (C36R, R164C, and R178C) do not adversely affect the global stability or fold of RyR(NTD), supporting previously described mechanisms whereby mutations perturb protein-protein interactions.

PubMed: 19541610
DOI: 10.1073/pnas.0905186106

実験手法

X-RAY DIFFRACTION (2.5 Å)