Nature chemical biology

How AcrIF24 works to block CRISPR and suppress gene activity

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated

Abstract

AcrIF24 binds to promoter DNA with nanomolar affinity.

  • AcrIF24 is a homodimer that associates with two copies of the CRISPR surveillance complex (Csy).
  • It inhibits the type I-F CRISPR-Cas system in Pseudomonas aeruginosa by preventing the hybridization of CRISPR RNA and target DNA.
  • AcrIF24 also acts as an anti-CRISPR-associated (Aca) protein, repressing the transcription of the acrIF23-acrIF24 operon.
  • The structure of the Csy-AcrIF24-promoter DNA complex at 2.7 Å reveals the mechanism for transcriptional suppression.
  • AcrIF24 functions as a fusion protein combining both Acr and Aca activities, highlighting the diverse mechanisms of Acr proteins.

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Funding

Competing interests

COMPETING INTERESTS. J.B.-D. is a scientific advisory board member of SNIPR Biome and Excision Biotherapeutics and a scientific advisory board member and co-founder of Acrigen Biosciences. The Bondy-Denomy lab receives research support from Felix Biotechnology. The remaining authors declare no competing interests.
PubMed

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