カルモジュリン依存グルタミラーゼによるフォスフォリボシルユビキチン化の調節
Ninghai Gan1, Xiangkai Zhen2,3, Yao Liu1
1Purdue Institute for Inflammation, Immunology and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
Nature
|July 23, 2019
まとめ
細菌の毒性を抑制するために,Legionella pneumophilaはエフェクタ SidJ を使用する. SidJは,宿主カルモジュリンを必要とするSdeAにグルタミン酸を結合し,新しい宿主因子依存の調節機構を明らかにします.
科学分野:
- 微生物学
- 分子生物学
- 生物化学
背景:
- レジオネラ・プネモフィラはドット/イクムエフェクターを使って宿主細胞を調節する.
- SidEファミリーのタンパク質は,独特のフォスフォリボシルユビキチン化によって細胞プロセスを調節する.
- SidJは,SideEの活動を調節するDot/Icmエフェクターですが,そのメカニズムは不明です.
研究 の 目的:
- SidJがSideファミリーエフェクターを調節するメカニズムを明らかにする.
- SidJによる調節における宿主因子の役割を調査する.
- SidJの構造的および生化学的基礎を特徴づける.
主な方法:
- サイト・ディレクテッド・ミュータジェネシスで,触媒の残留を特定する.
- 構造生物学 (X線結晶学) で,複雑な構造を決定する.
- 酵素活性と基質変化を評価する生化学的測定
主要な成果:
- SidJは,重要な触媒残留物 (E860) でSdeAのグルタミル化を触媒化することによって,SideEの活性を抑制する.
- SidJの活動は宿主タンパク質カルモジュリン (CaM) に依存し,その機能を真核細胞に制限する.
- SidJは,グルタミン酸またはSdeAが欠けると,アルファリン酸で割れ,ATPを使用して自己AMPylationの活性を示します.
結論:
- SidJは,細菌の毒性因子を抑制するために宿主因子依存のグルタミル化メカニズムを使用します.
- この発見は,宿主因子の活性化を含む細菌の病原性における新しい調節経路を明らかにしています.
- この発見は 細菌のエフェクターと宿主細胞の 複雑な相互作用の洞察を与えてくれます
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