ポリプレニルフォスファートトランスポーターの2つの広く保存されたファミリー
1Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Nature
|November 30, 2022
まとめ
研究者らは,バクテリアのアンデカプレニルリン酸 (UndP) のリサイクルに不可欠な2つのタンパク質ファミリー,UptAとPopTを特定しました. これらのUndPトランスポーターは細胞壁の合成に不可欠であり,新しい抗生物質の潜在的標的です.
科学分野:
- 細菌学
- 分子生物学
- 生物化学
背景:
- ペプチドグリカンを含む細菌の細胞表面ポリマーは,脂質キャリアとしてアンデカプレニルリン酸 (UndP) を使用して合成されます.
- UndPに結合した前駆物質は,ポリメリゼーションのために膜に運ばれ, UndPは細胞質に再利用されなければならない.
研究 の 目的:
- バクテリアの膜を横断して UndP の輸送と再利用を担当するフリッパースを特定する.
- バクテリアの細胞壁の生化に不可欠な UndP リサイクルメカニズムを理解する.
主な方法:
- UndPを標的とするアンフォミシン抗生物質を用いて UndPのリサイクルに関与する重要なタンパク質を特定した.
- 特定されたタンパク質ファミリーの機能を特徴づけるために遺伝的,細胞学的,合成的分析を行いました.
主要な成果:
- 2つの保存されたタンパク質ファミリー,UptA (DedA超ファミリー) とPopT (DUF368ドメイン) を,重要なUndPトランスポーターとして特定した.
- 様々なバクテリアからのUptAとPopTホモログがBacillus subtilisにおけるUndP輸送を容易にし,広範な機能的保存を示すことが示された.
結論:
- UptAとPopTは長い間求められてきたUndPフリップフェーズで,細菌の細胞封筒合成に不可欠です.
- これらのUndPトランスポーターを阻害剤で標的にすることで,既存の抗生物質の有効性を高めることができます.
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