4P9J

Crystal Structure of rabbit Ryanodine Receptor 1 SPRY2 Domain (1070-1246)

4P9J の概要

• エントリーDOI: 10.2210/pdb4p9j/pdb
• 関連するPDBエントリー: 4P9I
• 分子名称: Ryanodine receptor 1 (2 entities in total)
• 機能のキーワード: ion channel, calcium, metal transport, signalling, transport protein
• 由来する生物種: Oryctolagus cuniculus (Rabbit)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 60661.87

構造登録者

Lau, K.,Van Petegem, F. (登録日: 2014-04-04, 公開日: 2014-11-05, 最終更新日: 2023-12-27)

主引用文献

Lau, K.,Van Petegem, F.
Crystal structures of wild type and disease mutant forms of the ryanodine receptor SPRY2 domain.
Nat Commun, 5:5397-5397, 2014

PubMed Abstract: Ryanodine receptors (RyRs) form channels responsible for the release of Ca(2+) from the endoplasmic and sarcoplasmic reticulum. The SPRY2 domain in the skeletal muscle isoform (RyR1) has been proposed as a direct link with L-type calcium channels (CaV1.1), allowing for direct mechanical coupling between plasma membrane depolarization and Ca(2+) release. Here we present the crystal structures of the SPRY2 domain from RyR1 and RyR2 at 1.34-1.84 Å resolution. They form two antiparallel β sheets establishing a core, and four additional modules of which several are required for proper folding. A buried disease mutation, linked to hypertrophic cardiomyopathy and loss-of-function, induces local misfolding and strong destabilization. Isothermal titration calorimetry experiments negate the RyR1 SPRY2 domain as the major link with CaV1.1. Instead, docking into full-length RyR1 cryo-electron microscopy maps suggests that the SPRY2 domain forms a link between the N-terminal gating ring and the clamp region.

PubMed: 25370123
DOI: 10.1038/ncomms6397

実験手法

X-RAY DIFFRACTION (1.84 Å)