NOD2の活性化には,NAGKによるムラミルペプチドのリン酸化が必要です
Che A Stafford1, Alicia-Marie Gassauer1, Carina C de Oliveira Mann1
1Gene Center and Department of Biochemistry, Ludwig-Maximilians-Universität, Munich, Germany.
Nature
|August 24, 2022
まとめ
N-アセチルグルコサミンキナーゼ (NAGK) は,ムラミルディペプチド (MDP) のような細菌のペプチドグリカン成分を検出するために不可欠です. NAGKはMDPをリン酸化し,先天的な免疫受容体NOD2が細菌の細胞壁を感知し,免疫反応を誘発することを可能にします.
科学分野:
- 生まれつきの免疫
- 分子生物学
- 微生物学
背景:
- 細菌の細胞壁にはペプチドグリカン (PGN) が含まれており,これは先天的な免疫受容体によって認識される構造です.
- ムラミルダイペプチド (MDP) は,NOD2によって感知されるPGNの重要な免疫成分です.
- NOD2の活性化は,腸のバリア機能と炎症反応に不可欠です.
研究 の 目的:
- 生まれつきの免疫系によるMDP検出に関与する新しい要因を特定する.
- NOD2がMDPを感知するメカニズムを解明する.
- アミノ糖の代謝と 細菌の細胞壁の免疫の関係を理解する
主な方法:
- MDP検出に不可欠な遺伝子を特定するために遺伝子スクリーンを転送します.
- 特定された因子の酵素活性を決定する生化学的測定法.
- ノックアウト/欠乏細胞と動物モデルにおける免疫反応の分析
主要な成果:
- N- アセチルグルコサミンキナーゼ (NAGK) は,MDPの免疫刺激活性に不可欠であると特定されました.
- NAGKはMDPを直接リン酸化して6-O-フォスフォ-MDPを生成する.
- 6O-フォスフォ-MDPは,未修正のMDPではないが,NOD2に対するアゴニストとして作用する.
- NAGKが欠けているマクロファージはMDPを感知できません.
結論:
- NAGKはNOD2シグナリングの重要な上流調節器である.
- NAGKは,アミノ糖の代謝と細菌の免疫認識を結びつけています.
- この発見は 細菌の感染に対する 宿主の防御について 新たな洞察を与えてくれます
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