斯坦福大学Alex Gao团队取得一项新突破。他们的研究认为多种细菌模式识别受体感知核心噬菌体蛋白质组。该研究于2026年7月29日发表于国际一流学术期刊《自然》杂志上。

在这里，课题组研究人员对原核STAND NTPases进行了系统的系统发育分析，并确定了至少90个与抗病毒防御相关的结构不同的家族。课题组人员首先证明了未被鉴定的Avs7家族识别尾部噬菌体的主要衣壳蛋白（MCP）。大肠沙门氏菌Avs7的三个低温电子显微镜结构揭示了一个不对称的蝴蝶形四聚体，它通过MCP诱导的大构象变化逐步组装，其中包含细菌延伸因子Tu （EF-Tu）作为增强防御的结构成分。

利用687个噬菌体基因库的遗传筛选，研究组进一步发现13个额外的STAND家族可以感知13种保守的噬菌体蛋白，包括尾状噬菌体的大部分核心结构和复制成分。其中包括2个不同的MCP传感家族（Avs8和Avs10）和11个其他家族（Avs11-21），它们分别识别门、门接头、尾喷嘴、头尾连接器、尾终止子、尾管蛋白、尾组装伴侣、卷尺蛋白、DNA聚合酶、解旋酶/RecA型ATP酶和单链DNA退火蛋白。总之，他们的发现揭示了宿主因子再利用的机制，并建立了基于结构的模式识别作为细菌免疫的基本策略。

据悉，识别细胞内的外来分子对生命各个领域的免疫都至关重要。包括真核nod样受体在内的STAND NTPase超家族蛋白在这一过程中起着核心作用。在细菌和古细菌中，虽然有几个STAND家族感知噬菌体蛋白，但它们的功能多样性在很大程度上仍未被探索。

附：英文原文

Title: Diverse bacterial pattern recognition receptors sense the core phage proteome

Author: Lee, Hyunbin, Luengo-Woods, Sofia, Zhang, Jianxiu, Makarova, Kira S., Wolf, Yuri I., Chiu, Collin, Evans, Simone A., Chen, Junyi, Xiao, Haopeng, Feng, Liang, Koonin, Eugene V., Gao, Alex

Issue&Volume: 2026-07-29

Abstract: Recognition of foreign molecules inside cells is critical for immunity across all domains of life. Proteins of the STAND NTPase superfamily1,2, including eukaryotic NOD-like receptors, play a central role in this process3,4. In bacteria and archaea, although several STAND families sense phage proteins5,6,7,8,9, their functional diversity remains largely unexplored. Here we conduct a systematic phylogenetic analysis of prokaryotic STAND NTPases and identify at least 90 structurally distinct families associated with antiviral defence. We first show that the uncharacterized Avs7 family recognizes the major capsid protein (MCP) of tailed phages. Three cryogenic electron microscopy structures of Salmonella enterica Avs7 reveal an asymmetric, butterfly-shaped tetramer that assembles stepwise through large, MCP-induced conformational changes, incorporating bacterial elongation factor Tu (EF-Tu) as a structural component that enhances defence. Using genetic screens with a library of 687 phage genes, we further show that 13 additional STAND families sense 13 conserved phage proteins, encompassing most of the core structural and replicative components of tailed phages. These include 2 distinct MCP-sensing families (Avs8 and Avs10) and 11 others (Avs11–21), which recognize the portal, portal adaptor, tail nozzle, head–tail connector, tail terminator, tail tube protein, tail assembly chaperone, tape measure protein, DNA polymerase, helicase/RecA-type ATPase and single-stranded DNA annealing protein, respectively. Together, our findings reveal a mechanism of host-factor repurposing and establish structure-based pattern recognition as a fundamental strategy of bacterial immunity.

DOI: 10.1038/s41586-026-10852-6

Source: https://www.nature.com/articles/s41586-026-10852-6