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Evolutionary and functional classification of the CARF domain superfamily, key sensors in prokaryotic antivirus

Kira S Makarova1, Albertas Timinskas2, Yuri I Wolf1

  • 1National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD 20894, USA.

Nucleic Acids Research
|August 1, 2020
PubMed

Insights

CRISPR-associated Rossmann Fold (CARF) and SAVED domains are vital in bacterial antiphage defense systems (CBASS). This study classifies these domains, revealing diverse functions in cyclic oligonucleotide sensing and signaling pathways.

Area of Science:

  • Molecular Biology
  • Genomics
  • Biochemistry

Background:

  • CRISPR-associated Rossmann Fold (CARF) and SAVED domains are crucial for cyclic oligonucleotide-based antiphage signaling systems (CBASS).
  • These systems mediate bacterial defense against phages by inducing cell dormancy or death.
  • CARF domains are often integrated into Type III CRISPR-Cas systems, sensing cyclic oligoA (cOA) and activating effectors.

Purpose of the Study:

  • To conduct a comprehensive census and classification of CARF and SAVED domains across bacteria and archaea.
  • To elucidate the functional diversity and evolutionary relationships of these domains.
  • To predict the specific roles of CARF and SAVED domains in CBASS pathways.

Main Methods:

  • Comparative genome analysis of CARF and SAVED domains.
  • Sequence and structure-based classification of identified domains.
  • Bioinformatic predictions of domain functions and pathway associations.

Main Results:

  • A comprehensive census identified 10 major CARF families and several smaller groups.
  • Classification revealed variations in structural features, effector associations, and ring nuclease activity.
  • Comparative analysis predicted distinct functions, distinguishing sensor-only CARF domains from those with dual sensor/nuclease roles.

Conclusions:

  • CARF and SAVED domains exhibit significant functional and structural diversity within CBASS.
  • The study provides a framework for understanding the intricate mechanisms of bacterial antiphage defense.
  • Predicted functional assignments will guide future experimental investigations into these defense systems.

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