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Structure-guided discovery of anti-CRISPR and anti-phage defense proteins

Author

Listed:
  • Ning Duan

    (National Institutes of Health)

  • Emily Hand

    (National Institutes of Health)

  • Mannuku Pheko

    (National Institutes of Health)

  • Shikha Sharma

    (National Institutes of Health)

  • Akintunde Emiola

    (National Institutes of Health)

Abstract

Bacteria use a variety of defense systems to protect themselves from phage infection. In turn, phages have evolved diverse counter-defense measures to overcome host defenses. Here, we use protein structural similarity and gene co-occurrence analyses to screen >66 million viral protein sequences and >330,000 metagenome-assembled genomes for the identification of anti-phage and counter-defense systems. We predict structures for ~300,000 proteins and perform large-scale, pairwise comparison to known anti-CRISPR (Acr) and anti-phage proteins to identify structural homologs that otherwise may not be uncovered using primary sequence search. This way, we identify a Bacteroidota phage Acr protein that inhibits Cas12a, and an Akkermansia muciniphila anti-phage defense protein, termed BxaP. Gene bxaP is found in loci encoding Bacteriophage Exclusion (BREX) and restriction-modification defense systems, but confers immunity independently. Our work highlights the advantage of combining protein structural features and gene co-localization information in studying host-phage interactions.

Suggested Citation

  • Ning Duan & Emily Hand & Mannuku Pheko & Shikha Sharma & Akintunde Emiola, 2024. "Structure-guided discovery of anti-CRISPR and anti-phage defense proteins," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45068-7
    DOI: 10.1038/s41467-024-45068-7
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