8IY2

Structure of Acb2 complexed with 3',3'-cGAMP and cAAA

8IY2 の概要

• エントリーDOI: 10.2210/pdb8iy2/pdb
• 分子名称: p26, 1,2-ETHANEDIOL, [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] dihydrogen phosphate, ... (5 entities in total)
• 機能のキーワード: anti-cbass protein, viral protein
• 由来する生物種: Pseudomonas phage PaP2
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 73402.31

構造登録者

Cao, X.L.,Xiao, Y.,Feng, Y. (登録日: 2023-04-03, 公開日: 2024-02-07, 最終更新日: 2024-03-13)

主引用文献

Cao, X.,Xiao, Y.,Huiting, E.,Cao, X.,Li, D.,Ren, J.,Fedorova, I.,Wang, H.,Guan, L.,Wang, Y.,Li, L.,Bondy-Denomy, J.,Feng, Y.
Phage anti-CBASS protein simultaneously sequesters cyclic trinucleotides and dinucleotides.
Mol.Cell, 84:375-385.e7, 2024

PubMed Abstract: Cyclic-oligonucleotide-based anti-phage signaling system (CBASS) is a common immune system that uses cyclic oligonucleotide signals to limit phage replication. In turn, phages encode anti-CBASS (Acb) proteins such as Acb2, which can sequester some cyclic dinucleotides (CDNs) and limit downstream effector activation. Here, we identified that Acb2 sequesters many CDNs produced by CBASS systems and inhibits stimulator of interferon genes (STING) activity in human cells. Surprisingly, the Acb2 hexamer also binds with high affinity to CBASS cyclic trinucleotides (CTNs) 3'3'3'-cyclic AMP-AMP-AMP and 3'3'3'-cAAG at a distinct site from CDNs. One Acb2 hexamer can simultaneously bind two CTNs and three CDNs. Phage-encoded Acb2 provides protection from type III-C CBASS that uses cA signaling molecules. Moreover, phylogenetic analysis of >2,000 Acb2 homologs encoded by diverse phages and prophages revealed that most are expected to bind both CTNs and CDNs. Altogether, Acb2 sequesters nearly all known CBASS signaling molecules through two distinct binding pockets and therefore serves as a broad-spectrum inhibitor of cGAS-based immunity.

PubMed: 38103556
DOI: 10.1016/j.molcel.2023.11.026

実験手法

X-RAY DIFFRACTION (2.76 Å)