STIM1媒介による,倉庫でのカルシウム摂取開始に関する構造的およびメカニズム的洞察
Peter B Stathopulos1, Le Zheng, Guang-Yao Li
1Division of Signaling Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto Medical Discovery Tower, MaRS Centre, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
Cell
|October 16, 2008
まとめ
ストロマル相互作用分子-1 (STIM1) は,カルシウムのエントリーを調節する. そのCa2+感受性EF-SAM領域は,
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- ストロマル相互作用分子-1 (STIM1) は,ストア操作カルシウムエントリー (SOCE) の重要なレギュラーです.
- STIM1の活性化は,細胞内貯蔵中のカルシウム濃度の低下によって引き起こされます.
研究 の 目的:
- STIM1 Ca2+センシングEF-SAM領域の原子構造を決定する.
- STIM1媒介のSOCE開始の背後にある分子メカニズムを解明する.
主な方法:
- STIM1 EF-SAMドメインの原子構造を決定するためのX線結晶学.
- 特定の残留物とドメインの役割を調査するために,サイト指向型変異遺伝.
- 哺乳類の細胞における細胞ベースアッセイで,STIM1の機能とSOCEの活動を評価する.
主要な成果:
- STIM1 EF-SAM領域の原子構造は,SAM領域と相互作用するペア化されたEF-ハンドモチーフを明らかにしました.
- EFハンドまたはSAMドメインの相互作用を妨害する変異は,EF-SAMエンティティを不安定化し,Ca2+感受性とオリゴメリゼーションに影響を与えました.
- 完全な長さのSTIM1誘発点形成および細胞におけるCa2+独立のSOCE活性化における不安定化変異.
結論:
- STIM1 EF-SAM領域の折りたたまれた/開いた状態は,SOCE.を規制する上で極めて重要です.
- 原子レベルの構造的な洞察は,STIM1媒介のSOCEイニシアチブの分子基礎を説明します.
- EF-ハンドペアとSAMドメインの相互作用は,STIM1のCa2+感受性と機能に不可欠です.
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