8DRP

Focus/local refined map in C4 of signal subtracted RyR1 particles

8DRP の概要

• エントリーDOI: 10.2210/pdb8drp/pdb
• EMDBエントリー: 27680
• 分子名称: Ryanodine receptor 1, CAFFEINE, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: ryanodine receptor, ion channel, snake toxin, calcin, complex, membrane protein, toxin
• 由来する生物種: Oryctolagus cuniculus (rabbit)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 2266701.62

構造登録者

Haji-Ghassemi, O.,Van Petegm, F. (登録日: 2022-07-21, 公開日: 2023-05-31, 最終更新日: 2024-11-13)

主引用文献

Haji-Ghassemi, O.,Chen, Y.S.,Woll, K.,Gurrola, G.B.,Valdivia, C.R.,Cai, W.,Li, S.,Valdivia, H.H.,Van Petegem, F.
Cryo-EM analysis of scorpion toxin binding to Ryanodine Receptors reveals subconductance that is abolished by PKA phosphorylation.
Sci Adv, 9:eadf4936-eadf4936, 2023

PubMed Abstract: Calcins are peptides from scorpion venom with the unique ability to cross cell membranes, gaining access to intracellular targets. Ryanodine Receptors (RyR) are intracellular ion channels that control release of Ca from the endoplasmic and sarcoplasmic reticulum. Calcins target RyRs and induce long-lived subconductance states, whereby single-channel currents are decreased. We used cryo-electron microscopy to reveal the binding and structural effects of imperacalcin, showing that it opens the channel pore and causes large asymmetry throughout the cytosolic assembly of the tetrameric RyR. This also creates multiple extended ion conduction pathways beyond the transmembrane region, resulting in subconductance. Phosphorylation of imperacalcin by protein kinase A prevents its binding to RyR through direct steric hindrance, showing how posttranslational modifications made by the host organism can determine the fate of a natural toxin. The structure provides a direct template for developing calcin analogs that result in full channel block, with potential to treat RyR-related disorders.

PubMed: 37224245
DOI: 10.1126/sciadv.adf4936

実験手法

ELECTRON MICROSCOPY (2.84 Å)