CARF and WYL domains

Ligand-binding regulators of prokaryotic defense systems

Kira S. Makarova, Vivek Anantharaman, Nick V. Grishin, Eugene V. Koonin, L. Aravind

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

CRISPR-Cas adaptive immunity systems of bacteria and archaea insert fragments of virus or plasmid DNA as spacer sequences into CRISPR repeat loci. Processed transcripts encompassing these spacers guide the cleavage of the cognate foreign DNA or RNA. Most CRISPR-Cas loci, in addition to recognized cas genes, also include genes that are not directly implicated in spacer acquisition, CRISPR transcript processing or interference. Here we comprehensively analyze sequences, structures and genomic neighborhoods of one of the most widespread groups of such genes that encode proteins containing a predicted nucleotide-binding domain with a Rossmann-like fold, which we denote CARF (CRISPR-associated Rossmann fold). Several CARF protein structures have been determined but functional characterization of these proteins is lacking. The CARF domain is most frequently combined with a C-terminal winged helix-turn-helix DNA-binding domain and "effector" domains most of which are predicted to possess DNase or RNase activity. Divergent CARF domains are also found in RtcR proteins, sigma-54 dependent regulators of the rtc RNA repair operon. CARF genes frequently co-occur with those coding for proteins containing the WYL domain with the Sm-like SH3 β-barrel fold, which is also predicted to bind ligands. CRISPR-Cas and possibly other defense systems are predicted to be transcriptionally regulated by multiple ligand-binding proteins containing WYL and CARF domains which sense modified nucleotides and nucleotide derivatives generated during virus infection. We hypothesize that CARF domains also transmit the signal from the bound ligand to the fused effector domains which attack either alien or self nucleic acids, resulting, respectively, in immunity complementing the CRISPR-Cas action or in dormancy/programmed cell death.

Original languageEnglish (US)
Article numberArticle 102
JournalFrontiers in Genetics
Volume5
Issue numberAPR
DOIs
StatePublished - 2014

Fingerprint

Clustered Regularly Interspaced Short Palindromic Repeats
Ligands
Nucleotides
Proteins
RNA
Genes
Intergenic DNA
Deoxyribonucleases
DNA
Archaea
Adaptive Immunity
Virus Diseases
Operon
Ribonucleases

Keywords

  • Beta barrel
  • CRISPR
  • DNA-binding proteins
  • Phage defense
  • Rossmann fold

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Genetics(clinical)

Cite this

CARF and WYL domains : Ligand-binding regulators of prokaryotic defense systems. / Makarova, Kira S.; Anantharaman, Vivek; Grishin, Nick V.; Koonin, Eugene V.; Aravind, L.

In: Frontiers in Genetics, Vol. 5, No. APR, Article 102, 2014.

Research output: Contribution to journalArticle

Makarova, Kira S. ; Anantharaman, Vivek ; Grishin, Nick V. ; Koonin, Eugene V. ; Aravind, L. / CARF and WYL domains : Ligand-binding regulators of prokaryotic defense systems. In: Frontiers in Genetics. 2014 ; Vol. 5, No. APR.
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