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配列モチーフ認識による標的選択タンパク質S-ニトロシル化
Jie Jia1, Abul Arif1, Fulvia Terenzi1
1Department of Cellular and Molecular Medicine, The Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Cell
|November 24, 2014
まとめ
研究者らは,酸化窒素 (NO) を使用してタンパク質を改変する新しいタンパク質複合体を発見しました. この複合体は,誘導性酸化窒素合成酵素 (iNOS),S100A8,S100A9を含むもので,特定のタンパク質の部位を正確に標的にし,リン酸化に似ています.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 細胞シグナル伝達 細胞信号伝達
背景:
- S-ニトロシライゼーションは,細胞機能を調節する重要な酸化窒素 (NO) 媒介の翻訳後の改変である.
- 多くのS-ニトロシル化タンパク質が知られているが,酵素 (S-ニトロシラーゼ) とサイト選択的改変のメカニズムは,ほとんど特徴づけられていない.
研究 の 目的:
- 新種のS-ニトロシラーゼ複合体を特定し,特徴づけること.
- サイト選択性S-ニトロシル化に基づくメカニズムを解明する.
- S-ニトロシルアゼによって認識される配列モチーフを特定するために.
主な方法:
- S-ニトロシル化タンパク質を特定するためのプロテオミック分析.
- 酵素の活性と複合体の形成を特徴付けるための生化学的分析.
- 特定の配列モチーフの役割を決定するサイト指向型変異.
主要な成果:
- 誘導性酸化窒素合成酵素 (iNOS),S100A8,S100A9の新型ヘトロトリメリック複合体は,刺激誘導性S-ニトロシラーゼとして特定されました.
- S100A9はトランスニトロシラーゼとして作用し,iNOSからNOを標的タンパク質に転送します.
- S100A8とS100A9は,保存されたI/L-X-C-X2-D/Eモチーフを認識して,サイト選択を直接するために協力します.
- プロテオミック分析により,このiNOS-S100A8/A9複合体の新しいタンパク質標的が特定されました.
結論:
- iNOS-S100A8/A9複合体は,刺激に依存したS-ニトロシル化の主なメカニズムです.
- 特定の配列モチーフによって媒介されるサイト選択的S-ニトロシル化は,タンパク質リン酸化のメカニズムに並行する.
- この発見は,NOシグナル伝達経路とタンパク質の調節に関する新しい洞察を提供します.
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