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CBASS免疫は,CARFに関連するエフェクターを使用して,3'-5'-および2'-5'-リンクされた周期性オリゴヌクレオチド信号を感知し,細菌をファグ感染から保護します

Brianna Lowey¹, Aaron T Whiteley¹, Alexander F A Keszei²

¹Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

|June 17, 2020

まとめ

研究者らは,CD-NTase信号の受容体として作用する細菌のタンパク質であるCap4を発見しました. このタンパク質ファミリーは,特定の周期的な核酸二次伝達物質を認識することによって,細菌の免疫防御に重要な役割を果たします.

科学分野:

微生物学
免疫学
構造生物学

背景:

循環型GMP-AMP合成酵素/DncV型核チルトランスファーゼ (CD-NTase) 酵素は,細菌や動物の先天性免疫に不可欠であり,第2伝達核チロイドを合成して防御反応を誘発する.
細菌のCD-NTアゼは抗ウイルス防御を含む様々な細胞プロセスに関与しますが信号を感知する受容体はほとんど特徴づけられていないままです

研究の目的:

CD-NTaseで合成された核酸二次伝達物質に反応する新しい細菌受容体を特定し,特徴づけること.
この新発見された受容体の構造と作用機構を明らかにする.

主な方法:

Cap4の高解像度構造を決定するための構造生物学技術 (X線結晶学)
Cap4および関連するタンパク質の結合特性および酵素活性を調査する生化学的測定法.
細菌種間のCAP4型タンパク質の流行と多様性を特定するためのバイオ情報分析.

主要な成果:

バクテリアのCD-NTase信号受容体の大家族 (>2,000人) の代表者として,Enterobacter cloacaeのCD-NTase関連タンパク質4 (Cap4) の発見.
Cap4の構造的決定は,DNAエンドヌクレアースドメインと付属のSAVEDドメインを明らかにし,CRISPRに関連した2つのロスマン折り (CARF) サブユニットの融合である.
SAVEDドメインは,サイクルオリゴヌクレオチドセカンドメッセンジャーの異なる結合同位体 (2'-5'および3'-5') を特定して区別し,少なくとも180の異なる種を検出することを証明する.

結論:

SAVED CARFファミリーのタンパク質は,細菌のサイクルヌクレオチドベースの適応システム (CBASS) とCRISPR- Cas免疫システムにおける核酸二次伝達物質の主要な受容体として特定されています.
この発見は,受容体-リガンドの相互作用における結合特異性の重要な役割を強調し,この原理を哺乳類のcGAS-STINGシグナル伝達を超えて拡張します.
この研究は細菌の先天的な免疫とニュクレオチド二次メッセンジャーシグナル伝達経路の多様性に関する理解を広げています

キーワード:

カーフ CBASS抗菌体に対する免疫 CD-NT 酵素 SAVED (救った)核酸二次メッセンジャー

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