Yersinia YopJは,リン酸化を阻害することによってアセチラ化し,キナーゼ活性化を阻害する
Sohini Mukherjee1, Gladys Keitany, Yan Li
1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science (New York, N.Y.)
|May 27, 2006
まとめ
イエルシニア (Yersinia) とは
科学分野:
- 微生物学と分子生物学について
- 細胞信号伝達と免疫学
背景:
- イエルシニア種は,宿主の真核細胞の信号伝達経路を妨害するために,III型エフェクタータンパク質を使用します.
- ミトゲン活性化タンパク質キナーゼ (MAPK) と核因子カッパB (NFkappaB) を含む重要な先天的免疫経路は,イエルシニアエフェクターによって標的にされています.
- YersiniaエフェクターYopJは,MAPKキナーゼ (MAPKKs) の活性化を阻害することによって,MAPKとNFkappaBのシグナル伝達を特に抑制する.
研究 の 目的:
- YersiniaエフェクターYopJがMAPKKの活性化を阻害する分子メカニズムを解明する.
- YopJの酵素活性と,MAPKKタンパク質の改変におけるYopJの役割を調査する.
- YopJ媒介による改変がMAPKKsのリン酸化と活性化にどのように影響するかを理解する.
主な方法:
- YopJ.の酵素活性を決定する生化学的分析.
- YopJとアセチル-コエンザイムA (CoA) を使用したMAPKK6のインビトロ改変.
- MAPKK6の活性化ループにおけるセリンとスレオニン残留物の変化の分析.
- MAPKK6のリン酸化と活性化に対するYopJ変更の影響の評価.
主要な成果:
- YopJはアセチルトランスフェラーゼとして機能し,アセチル-コアを使用します.
- YopJは,MAPKK6.6の活性化ループ内の重要なセリンおよびセロニン残基をアセチル化します.
- YopJによるアセチル化は,MAPKK6のリン酸化と直接競合し,それを阻害し,MAPKK6の活性化を阻害する.
結論:
- YersiniaのYopJエフェクターは,MAPKKの活性化をアセチル化およびブロックすることにより,宿主の先天的な免疫シグナリングを阻害します.
- このアセチル化メカニズムは,フォスフォリレーションの直接的な競争的阻害として機能し,下流シグナリングを防止します.
- アセチル化による共性変異は,生物学的シグナル伝達経路における潜在的な一般的な規制メカニズムを表しています.
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