6X34

Pig R615C RyR1 EGTA (all classes, open)

6X34 の概要

• エントリーDOI: 10.2210/pdb6x34/pdb
• EMDBエントリー: 22015 22016 22017 22018 22019
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP1B, Ryanodine Receptor, ZINC ION (3 entities in total)
• 機能のキーワード: receptor, calcium, channel, complex, transport protein-isomerase complex, transport protein/isomerase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 1704401.90

構造登録者

Woll, K.W.,Haji-Ghassemi, O.,Van Petegem, F. (登録日: 2020-05-21, 公開日: 2021-01-13, 最終更新日: 2024-03-06)

主引用文献

Woll, K.A.,Haji-Ghassemi, O.,Van Petegem, F.
Pathological conformations of disease mutant Ryanodine Receptors revealed by cryo-EM.
Nat Commun, 12:807-807, 2021

PubMed Abstract: Ryanodine Receptors (RyRs) are massive channels that release Ca from the endoplasmic and sarcoplasmic reticulum. Hundreds of mutations are linked to malignant hyperthermia (MH), myopathies, and arrhythmias. Here, we explore the first MH mutation identified in humans by providing cryo-EM snapshots of the pig homolog, R615C, showing that it affects an interface between three solenoid regions. We also show the impact of apo-calmodulin (apoCaM) and how it can induce opening by bending of the bridging solenoid, mediated by its N-terminal lobe. For R615C RyR1, apoCaM binding abolishes a pathological 'intermediate' conformation, distributing the population to a mixture of open and closed channels, both different from the structure without apoCaM. Comparisons show that the mutation primarily affects the closed state, inducing partial movements linked to channel activation. This shows that disease mutations can cause distinct pathological conformations of the RyR and facilitate channel opening by disrupting interactions between different solenoid regions.

PubMed: 33547325
DOI: 10.1038/s41467-021-21141-3

実験手法

ELECTRON MICROSCOPY (4.7 Å)