ArticleProceedings of the National Academy of Sciences of the United States of America2023
The structural basis of hyperpromiscuity in a core combinatorial network of type II toxin-antitoxin and related phage defense systems.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed.
- Comparative essentialome analysis of sixMicrobial genomics · 2026Article
- A genomic catalog of the mouse gut virome reveals features associated with ageing.Nature communications · 2026Article
- Nuclease-NTPase antiphage defence systems use conserved molecular features to control bacterial immunity.Nature microbiology · 2026Article
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- Protein structure-informed bacteriophage genome annotation with Phold.Nucleic acids research · 2026Article
- Viral Dark Matter: Illuminating Protein Function, Ecology, and Biotechnological Promises.Biochemistry · 2025Review
- A toxin/antitoxin system targeting the replication sliding-clamp induces competence in Streptococcus pneumoniae.PLoS genetics · 2025Article
- The Viral AlphaFold Database of monomers and homodimers reveals conserved protein folds in viruses of bacteria, archaea, and eukaryotes.Science advances · 2025Article
- A minimal model of panimmunity maintenance by horizontal gene transfer in the ecological dynamics of bacteria and phages.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fold first, ask later: structure-informed function annotation ofbioRxiv : the preprint server for biology · 2025Article
- Unveiling the multifaceted domain polymorphism of the Menshen antiphage system.Nucleic acids research · 2025Article
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- Factors Affecting Phage-Bacteria Coevolution Dynamics.Viruses · 2025Review
- Mechanisms of neutralization of toxSAS from toxin-antitoxin modules.Nature chemical biology · 2025Article
- "French Phage Network" annual conference: ninth meeting report.microLife · 2025Article
- Gamma-Mobile-Trio systems are mobile elements rich in bacterial defensive and offensive tools.Nature microbiology · 2024Article
- Conformational change as a mechanism for toxin activation in bacterial toxin-antitoxin systems.Journal of virology · 2024Review
- Article
- Identification of type VI secretion system effector-immunity pairs using structural bioinformatics.Molecular systems biology · 2024Article
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22 authors.
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Abstract
Toxin-antitoxin (TA) systems are a large group of small genetic modules found in prokaryotes and their mobile genetic elements. Type II TAs are encoded as bicistronic (two-gene) operons that encode two proteins: a toxin and a neutralizing antitoxin. Using our tool NetFlax (standing for Network-FlaGs for toxins and antitoxins), we have performed a large-scale bioinformatic analysis of proteinaceous TAs, revealing interconnected clusters constituting a core network of TA-like gene pairs. To understand the structural basis of toxin neutralization by antitoxins, we have predicted the structures of 3,419 complexes with AlphaFold2. Together with mutagenesis and functional assays, our structural predictions provide insights into the neutralizing mechanism of the hyperpromiscuous Panacea antitoxin domain. In antitoxins composed of standalone Panacea, the domain mediates direct toxin neutralization, while in multidomain antitoxins the neutralization is mediated by other domains, such as PAD1, Phd-C, and ZFD. We hypothesize that Panacea acts as a sensor that regulates TA activation. We have experimentally validated 16 NetFlax TA systems and used domain annotations and metabolic labeling assays to predict their potential mechanisms of toxicity (such as membrane disruption, and inhibition of cell division or protein synthesis) as well as biological functions (such as antiphage defense). We have validated the antiphage activity of a RosmerTA system encoded by
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