4I3N

Crystal structure of rabbit ryanodine receptor 1 (residues 1-536) disease mutant D61N

4I3N の概要

• エントリーDOI: 10.2210/pdb4i3n/pdb
• 関連するPDBエントリー: 2XOA 4I0Y 4I1E 4I2S 4I37 4I6I 4I7I 4I8M 4I96
• 分子名称: Ryanodine receptor 1, GLYCEROL (3 entities in total)
• 機能のキーワード: calcium channel, sr/er membrane, metal transport
• 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: 1
• 化学式量合計: 59567.49

構造登録者

Kimlicka, L.,Van Petegem, F. (登録日: 2012-11-26, 公開日: 2013-02-20, 最終更新日: 2023-09-20)

主引用文献

Kimlicka, L.,Lau, K.,Tung, C.C.,Van Petegem, F.
Disease mutations in the ryanodine receptor N-terminal region couple to a mobile intersubunit interface.
Nat Commun, 4:1506-1506, 2013

PubMed Abstract: Ryanodine receptors are large channels that release Ca(2+) from the endoplasmic and sarcoplasmic reticulum. Hundreds of RyR mutations can cause cardiac and skeletal muscle disorders, yet detailed mechanisms explaining their effects have been lacking. Here we compare pseudo-atomic models and propose that channel opening coincides with widening of a cytoplasmic vestibule formed by the N-terminal region, thus altering an interface targeted by 20 disease mutations. We solve crystal structures of several disease mutants that affect intrasubunit domain-domain interfaces. Mutations affecting intrasubunit ionic pairs alter relative domain orientations, and thus couple to surrounding interfaces. Buried disease mutations cause structural changes that also connect to the intersubunit contact area. These results suggest that the intersubunit contact region between N-terminal domains is a prime target for disease mutations, direct or indirect, and we present a model whereby ryanodine receptors and inositol-1,4,5-trisphosphate receptors are activated by altering domain arrangements in the N-terminal region.

PubMed: 23422674
DOI: 10.1038/ncomms2501

実験手法

X-RAY DIFFRACTION (2.95 Å)