サイクルADPリボースイソマー:生産,化学構造,免疫シグナル伝達

Mohammad K Manik^1,2, Yun Shi³, Sulin Li^1,2

¹School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.

Science (New York, N.Y.)

|September 1, 2022

まとめ

循環性アデノシン二酸化物 (ADP) -リボス (cADPR) イソメアは,細菌および植物TIRドメインによって生成されます. これらの分子には,

科学分野:

生物化学
分子生物学
微生物学

背景:

循環性アデノシン二酸化物 (ADP) -リボース (cADPR) のイソメアはシグナル伝達分子である.
バクテリアと植物のトール/インタールイキン-1受容体 (TIR) ドメインは,ニコチナミドアデニン・ディヌクレオチド (酸化形態) (NAD+) の水解によってcADPRイソマーを生成する.

研究の目的:

TIRドメインによるcADPR同位体生成の分子メカニズムを解明する.
バクテリアと植物のシステムにおけるcADPRイソメアの生物学的な役割を調査する.

主な方法:

2'cADPRを生成するTIR領域の構造分析
サイト・ディレクテッド・ミュータジェネシスで,サイクライゼーションの鍵となる残基を特定する.
3'cADPRの活性を決定する生化学的測定.

主要な成果:

v-cADPR (2'cADPR) とv2-cADPR (3'cADPR) のイソメアは,ADPRにおけるリボース分子の間のO-グリコシド結合形成によって形成される.
TIRドメインの構造は,アクティブアセンブリにつながる形状の変化を明らかにします.
保存されたトリプトファンの残留はcADPRサイクリングに不可欠です.
3'cADPRは,トエリス系におけるバクテリアのThsAエフェクタータンパク質を活性化する.
3'cADPRは,HopAM1エフェクタによって生成される植物免疫を抑制する.

結論:

この研究は,TIRドメインによるcADPR同位体合成の分子基盤を明らかにしている.
3'cADPRは細菌における抗ウイルス信号分子として機能する.
3'cADPRは植物免疫抑制剤として作用する.

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