5C33

Crystal Structure of Mouse Ryanodine Receptor 2 SPRY1 Domain

5C33 の概要

• エントリーDOI: 10.2210/pdb5c33/pdb
• 関連するPDBエントリー: 5C30
• 分子名称: Ryanodine receptor 2, ISOPROPYL ALCOHOL, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: spry, ligand-binding, contractile protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44337.25

構造登録者

Yuchi, Z.,Van Petegem, F. (登録日: 2015-06-16, 公開日: 2015-08-05, 最終更新日: 2024-10-23)

主引用文献

Yuchi, Z.,Yuen, S.M.,Lau, K.,Underhill, A.Q.,Cornea, R.L.,Fessenden, J.D.,Van Petegem, F.
Crystal structures of ryanodine receptor SPRY1 and tandem-repeat domains reveal a critical FKBP12 binding determinant.
Nat Commun, 6:7947-7947, 2015

PubMed Abstract: Ryanodine receptors (RyRs) form calcium release channels located in the membranes of the sarcoplasmic and endoplasmic reticulum. RyRs play a major role in excitation-contraction coupling and other Ca(2+)-dependent signalling events, and consist of several globular domains that together form a large assembly. Here we describe the crystal structures of the SPRY1 and tandem-repeat domains at 1.2-1.5 Å resolution, which reveal several structural elements not detected in recent cryo-EM reconstructions of RyRs. The cryo-EM studies disagree on the position of SPRY domains, which had been proposed based on homology modelling. Computational docking of the crystal structures, combined with FRET studies, show that the SPRY1 domain is located next to FK506-binding protein (FKBP). Molecular dynamics flexible fitting and mutagenesis experiments suggest a hydrophobic cluster within SPRY1 that is crucial for FKBP binding. A RyR1 disease mutation, N760D, appears to directly impact FKBP binding through interfering with SPRY1 folding.

PubMed: 26245150
DOI: 10.1038/ncomms8947

実験手法

X-RAY DIFFRACTION (1.21 Å)