结构模型揭示了噬菌体蛋白操纵细菌免疫信号，这一成果由魏茨曼科学研究所Rotem Sorek研究组经过不懈努力而取得。相关论文发表在2026年3月5日出版的《科学》杂志上。

该研究组确定了多种病毒抗防御蛋白共有的结构和生物物理特征，并对这些特征进行了主题化，以开发一个计算管道，预测噬菌体蛋白的作用是操纵细菌免疫信号。实验验证揭示了三个以前未被表征的蛋白家族——Sequestin, Lockin, and Acb5，它们抑制Thoeris系统和基于环寡核苷酸的噬菌体信号系统（CBASS）。Sequestin和Lockin作为核苷酸“海绵”，结合1″- 3糖环腺苷二磷酸核糖（3cadpr）和与ADPR结合的组氨酸（His- ADPR），而Acb5则切割环鸟苷单磷酸腺苷一磷酸（3′3′-cGAMP）和相关分子。结构和突变分析解释了它们的结合和催化机制。在噬菌体基因组中存在同源物，这突出了病毒破坏基于核苷酸的免疫的策略的丰富性和多样性。

据介绍，动物、植物和细菌的免疫系统通常依赖于细胞内核苷酸信号，病毒主题可以通过隔离或降解这些信号来阻断这些信号。

附：英文原文

Title: Structural modeling reveals phage proteins that manipulate bacterial immune signaling

Author: Nitzan Tal, Romi Hadary, Renee B. Chang, Ilya Osterman, Roy Jacobson, Erez Yirmiya, Nathalie Bechon, Dina Hochhauser, Miguel López Rivera, Barak Madhala, Jeremy Garb, Moshe Goldsmith, Tanita Wein, Philip J. Kranzusch, Gil Amitai, Rotem Sorek

Issue&Volume: 2026-03-05

Abstract: Immune systems in animals, plants, and bacteria often rely on intracellular nucleotide signaling, which viruses can block by sequestering or degrading these signals. We identified structural and biophysical traits shared by diverse viral antidefense proteins and used these traits to develop a computational pipeline that predicts phage proteins whose role is to manipulate bacterial immune signaling. Experimental validation revealed three previously uncharacterized protein families—Sequestin, Lockin, and Acb5—that inhibit the Thoeris system and the cyclic oligonucleotide–based antiphage signaling system (CBASS). Sequestin and Lockin act as nucleotide “sponges,” binding 1″–3′ glycocyclic adenosine diphosphate–ribose (3′cADPR) and histidine conjugated to ADPR (His- ADPR), whereas Acb5 cleaves cyclic guanosine monophosphate–adenosine monosphosphate (3′3′-cGAMP) and related molecules. Structural and mutational analyses explain their binding and catalytic mechanisms. Thousands of homologs occur in phage genomes, highlighting the abundance and diversity of viral strategies to subvert nucleotide-based immunity.

DOI: aea1761

Source: https://www.science.org/doi/10.1126/science.aea1761