5CRH

Human skeletal calsequestrin, M53T mutant high-calcium complex

5CRH の概要

• エントリーDOI: 10.2210/pdb5crh/pdb
• 関連するPDBエントリー: 5CRD 5CRE 5CRG
• 分子名称: Calsequestrin-1, CALCIUM ION (3 entities in total)
• 機能のキーワード: calcium binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84467.08

構造登録者

Lewis, K.M.,Ronish, L.A.,Kang, C. (登録日: 2015-07-22, 公開日: 2015-10-07, 最終更新日: 2023-09-27)

主引用文献

Lewis, K.M.,Ronish, L.A.,Rios, E.,Kang, C.
Characterization of Two Human Skeletal Calsequestrin Mutants Implicated in Malignant Hyperthermia and Vacuolar Aggregate Myopathy.
J.Biol.Chem., 290:28665-28674, 2015

PubMed Abstract: Calsequestrin 1 is the principal Ca(2+) storage protein of the sarcoplasmic reticulum of skeletal muscle. Its inheritable D244G mutation causes a myopathy with vacuolar aggregates, whereas its M87T "variant" is weakly associated with malignant hyperthermia. We characterized the consequences of these mutations with studies of the human proteins in vitro. Equilibrium dialysis and turbidity measurements showed that D244G and, to a lesser extent, M87T partially lose Ca(2+) binding exhibited by wild type calsequestrin 1 at high Ca(2+) concentrations. D244G aggregates abruptly and abnormally, a property that fully explains the protein inclusions that characterize its phenotype. D244G crystallized in low Ca(2+) concentrations lacks two Ca(2+) ions normally present in wild type that weakens the hydrophobic core of Domain II. D244G crystallized in high Ca(2+) concentrations regains its missing ions and Domain II order but shows a novel dimeric interaction. The M87T mutation causes a major shift of the α-helix bearing the mutated residue, significantly weakening the back-to-back interface essential for tetramerization. D244G exhibited the more severe structural and biophysical property changes, which matches the different pathophysiological impacts of these mutations.

PubMed: 26416891
DOI: 10.1074/jbc.M115.686261

実験手法

X-RAY DIFFRACTION (2.03 Å)