ストレスセンサであるPDZプロテアゼであるDegSのアロステリック活性化
Jungsan Sohn1, Robert A Grant, Robert T Sauer
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell
|November 6, 2007
まとめ
外膜タンパク質 (OMP) 結合は,アロステリックメカニズムを通じてDegSプロテアゼを活性化し,機能状態に切り替えます. このスイッチのような行動は,E. coliの信号伝達に極めて重要です.
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.
- 細胞生物学 細胞生物学
背景:
- 調節された膜内タンパク質分解 (RIP) は,細胞区間の重要なシグナル伝達機構である.
- E. coliでは,損傷したペリプラズマタンパク質の折りたたみにより,外膜タンパク質 (OMP) によってDegSプロテアゼの活性化が誘発されます.
- DegSは,トランスメブランの調節体であるRseAを分割し,シグナルキャスケードを開始します.
研究 の 目的:
- OMPによるDegSプロテアゼ活性化のアロステリックメカニズムを解明する.
- DegSのスイッチのような振る舞いの構造的および機能的基礎を理解するために.
- 関連プロテアゼにおけるこのアロステル活性化メカニズムの保存を調査する.
主な方法:
- X線結晶学により,DegS構造を決定する.
- プロテアゼの活性を測定するための生化学的測定法.
- ミュタゲネーシス研究で,アロステル調節に関与する主要な残留物を特定する.
主要な成果:
- DegSはアロステル酵素として機能し,OMP結合時に無活性から活性型に変換します.
- DegSの非結合PDZドメインは阻害性であり,OMP結合は活性コンフォームを安定させる.
- OMP誘発の活性化とRseAの結合は,どちらもポジティブな協力性を示し,スイッチのような反応を可能にします.
- 主要なアロステル残基は,DegP/HtrAおよびHtrA2/Omiプロテアゼファミリーに保存されています.
結論:
- OMPの結合は,DegSプロテアゼをアロステリックに活性化するのに十分である.
- OMP-DegS-RseAシステムは,正の協力性により,スイッチのような性質を表示しています.
- 共通のアロステル活性化メカニズムは,多くのPDZプロテアゼの機能の根底にある可能性が高い.
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