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バクテリアのユビキチン・リガゼをSidJ-カルモジュリン触媒によるグルタミレーションによって抑制する
Sagar Bhogaraju1,2,3, Florian Bonn4, Rukmini Mukherjee4,5
1Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany. bhogaraju@embl.fr.
Nature
|July 23, 2019
まとめ
レジオネラ・プネモフィラの毒性は,SIDE酵素に依存しています. SidJは,カルモジュリンとカルシウムイオンを必要とするプロセスである,その触媒性グルタミン酸を改変することによって,SideEを無効化するグルタミラーゼとして作用します.
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,ユビキチン化と感染性のためにSIDE酵素を使用します.
- SidJはSideEの毒性に対抗しますが,そのメカニズムは不明でした.
- SidJは宿主細胞のレギオネラ増殖に不可欠です.
研究 の 目的:
- SidEの活動に対するSidJのメカニズムを解明する.
- グルタミラーゼとして特徴付けます
- SidJ機能におけるカルモジュリンとカルシウムの役割を探求する.
主な方法:
- SidJの酵素活性を特定するための生化学分析
- クリオ電子顕微鏡でSidJ-カルモジュリン複合体の構造を決定する.
- 定量プロテオミクスはSIDJの標的を特定する
主要な成果:
- SidJは,SdeAの触媒性グルタミン酸を修正し,そのリガース活性を抑制するグルタミラーゼです.
- SidJの活動はカルモジュリンと細胞内カルシウムに依存する.
- 構造分析により,ヘテロジメのグルタミラーゼ構造が明らかになった.
- SidJはレギオネラを含む真空中に SidE酵素をグルタミレートする.
- プロテオミクスは宿主タンパク質を潜在的SidJ標的として特定した.
結論:
- SidJはカルモジュリン依存型グルタミレーションによってSide結合酵素を阻害する.
- この研究は,細菌のエフェクター調節の新しいメカニズムを明らかにしています.
- グルタミライゼーションは研究されていない真核生物の変異である.
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