8VK3

Structure of mouse RyR1 in complex with S100A1 (EGTA-only dataset)

これはPDB形式変換不可エントリーです。

8VK3 の概要

• エントリーDOI: 10.2210/pdb8vk3/pdb
• EMDBエントリー: 43299
• 分子名称: Ryanodine receptor 1, Peptidyl-prolyl cis-trans isomerase FKBP1A, Protein S100A1, ... (5 entities in total)
• 機能のキーワード: calcium, ion channel, membrane protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 2401221.64

構造登録者

Weninger, G.,Marks, A.R. (登録日: 2024-01-08, 公開日: 2024-01-24, 最終更新日: 2024-10-16)

主引用文献

Weninger, G.,Miotto, M.C.,Tchagou, C.,Reiken, S.,Dridi, H.,Brandenburg, S.,Riedemann, G.C.,Yuan, Q.,Liu, Y.,Chang, A.,Wronska, A.,Lehnart, S.E.,Marks, A.R.
Structural insights into the regulation of RyR1 by S100A1.
Proc.Natl.Acad.Sci.USA, 121:e2400497121-e2400497121, 2024

PubMed Abstract: S100A1, a small homodimeric EF-hand Ca-binding protein (~21 kDa), plays an important regulatory role in Ca signaling pathways involved in various biological functions including Ca cycling and contractile performance in skeletal and cardiac myocytes. One key target of the S100A1 interactome is the ryanodine receptor (RyR), a huge homotetrameric Ca release channel (~2.3 MDa) of the sarcoplasmic reticulum. Here, we report cryoelectron microscopy structures of S100A1 bound to RyR1, the skeletal muscle isoform, in absence and presence of Ca. Ca-free apo-S100A1 binds beneath the bridging solenoid (BSol) and forms contacts with the junctional solenoid and the shell-core linker of RyR1. Upon Ca-binding, S100A1 undergoes a conformational change resulting in the exposure of the hydrophobic pocket known to serve as a major interaction site of S100A1. Through interactions of the hydrophobic pocket with RyR1, Ca-bound S100A1 intrudes deeper into the RyR1 structure beneath BSol than the apo-form and induces sideways motions of the C-terminal BSol region toward the adjacent RyR1 protomer resulting in tighter interprotomer contacts. Interestingly, the second hydrophobic pocket of the S100A1-dimer is largely exposed at the hydrophilic surface making it prone to interactions with the local environment, suggesting that S100A1 could be involved in forming larger heterocomplexes of RyRs with other protein partners. Since S100A1 interactions stabilizing BSol are implicated in the regulation of RyR-mediated Ca release, the characterization of the S100A1 binding site conserved between RyR isoforms may provide the structural basis for the development of therapeutic strategies regarding treatments of RyR-related disorders.

PubMed: 38917010
DOI: 10.1073/pnas.2400497121

実験手法

ELECTRON MICROSCOPY (3.21 Å)