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バクテリアに由来するSTINGサイクルディヌクレオチドセンシング
Benjamin R Morehouse1,2, Apurva A Govande1,2, Adi Millman3
1Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Nature
|September 3, 2020
まとめ
免疫に不可欠なインターフェロン遺伝子の刺激 (STING) 経路は,古代からバクテリアに由来しています. 研究者達は 機能的な細菌性STINGを発見し ウイルスや細菌に対する 生まれつきの免疫における 保存された役割を明らかにしました
科学分野:
- 免疫学
- 構造生物学
- 進化生物学
背景:
- インターフェロン遺伝子の刺激剤 (STING) は,ヒトの先天性免疫における重要な受容体であり,感染中に循環性ダイヌクレオチドを感知する.
- その独特な構造は,その起源と哺乳類における周期性ダイヌクレオチド信号伝達の理解を妨げています.
研究 の 目的:
- STING信号の進化的起源と機能的メカニズムを調査する.
- プロカリオットにおけるSTINGを含む保存されたシグナル伝達経路を解明する.
主な方法:
- バクテリアのSTING同類体の結晶構造の決定
- バクテリアとメタゾーンSTINGの比較構造分析
- STING獲得における進化的出来事を再構築する
主要な成果:
- 保存された活性化メカニズムを持つプロカリオット防衛島における機能的なSTING同類種を特定した.
- バクテリアのSTINGの構造を決定し, 周期的なdi-GMPに反応する最小の支架を明らかにしました.
- 抗ウイルス転写調節のためにメタゾーンSTINGがどのように進化したかを示した.
結論:
- 循環型GMP-AMP合成酵素 (cGAS) -STING経路は,バクテリオファージに対する防御のためにプロカリオットに保存されます.
- バクテリアのSTINGは,周期性ダイヌクレオチド認識とフィラメント形成を含む保存されたメカニズムを使用します.
- メタゾーンSTINGは プロカリオット起源から進化し 複雑な免疫調節に適応した
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