Diverse bacterial pattern recognition receptors sense the core phage proteome
8 affiliations
- 1Department of Biochemistry, Stanford University, Stanford, CA, USA
- 2Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA
- 3Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA
- 4Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
- 5Department of Genetics, Stanford University, Stanford, CA, USA
- 6Stanford Cancer Institute, Stanford University, Stanford, CA, USA
- 7Department of Biochemistry, Stanford University, Stanford, CA, USA. [email protected]
- 8Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA. [email protected]
Abstract
Recognition of foreign molecules inside cells is critical for immunity across all domains of life. Proteins of the STAND NTPase superfamily 1,2 , including eukaryotic NOD-like receptors, play a central role in this process 3,4 . In bacteria and archaea, although several STAND families sense phage proteins 5–9 , 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.
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BibTeX
@article{lee2026diverse,
title = {{Diverse bacterial pattern recognition receptors sense the core phage proteome}},
author = {Hyunbin Lee and Sofia Luengo-Woods and Jianxiu Zhang and Kira S. Makarova and Yuri I. Wolf and Collin Chiu and Simone A. Evans and Junyi Chen and Haopeng Xiao and Liang Feng and Eugene V. Koonin and Linyi Gao},
journal = {Nature},
year = {2026},
month = jul,
doi = {10.1038/s41586-026-10852-6},
url = {https://doi.org/10.1038/s41586-026-10852-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - Diverse bacterial pattern recognition receptors sense the core phage proteome
AU - Hyunbin Lee
AU - Sofia Luengo-Woods
AU - Jianxiu Zhang
AU - Kira S. Makarova
AU - Yuri I. Wolf
AU - Collin Chiu
AU - Simone A. Evans
AU - Junyi Chen
AU - Haopeng Xiao
AU - Liang Feng
AU - Eugene V. Koonin
AU - Linyi Gao
PY - 2026
DA - 2026/07/29
JO - Nature
DO - 10.1038/s41586-026-10852-6
UR - https://doi.org/10.1038/s41586-026-10852-6
AB - Recognition of foreign molecules inside cells is critical for immunity across all domains of life. Proteins of the STAND NTPase superfamily 1,2 , including eukaryotic NOD-like receptors, play a central role in this process 3,4 . In bacteria and archaea, although several STAND families sense phage proteins 5–9 , 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.
SN - 0028-0836
SN - 1476-4687
ER -