Regulation of anti-CRISPR operons by structurally distinct families of Aca proteins

Nov 26, 2025Communications biology

Control of anti-CRISPR gene groups by different types of Aca proteins

AI simplified

CRISPR Gene Editing on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Crystal structures reveal that Aca7 and Aca11 utilize distinct mechanisms for DNA binding.

Aca7 forms a symmetrical dimer to recognize a 19-bp within its operon.
Aca11 binds 22-bp inverted repeats in two different promoters, indicating its ability to control multiple operons.
Dimerization and specific recognition of inverted repeats are crucial for the DNA binding function of Aca proteins.
Despite similarities in monomer structures, the dimeric forms of Aca proteins show significant structural differences.
These variations in structure may enable Aca proteins to interact with different promoters and regulate various proteins.

AI simplified

CRISPR-Cas systems provide bacteria with adaptive immunity against bacteriophages and mobile genetic elements, driving an evolutionary arms race in which phages deploy anti-CRISPR () proteins. Acr proteins are often co-encoded in operons with anti-CRISPR-associated (Aca) proteins, which coordinate the regulation of acr gene expression. Here, we reveal the molecular basis of DNA binding that mediates transcriptional repression by two distinct Aca family members: Aca7 and Aca11. Crystal structures of Aca7 and Aca11 highlight conserved helix-turn-helix (HTH) motifs within α-helix bundles, providing a universal DNA-binding platform. Aca7 forms a symmetrical dimer to recognize a 19-bp (IR) within the acrIF11-aca7 operon. Strikingly, Aca11 binds 22-bp IRs in two distinct promoters, suggesting that Aca proteins can control multiple target operons. Mutagenesis and electrophoretic mobility shift assays (EMSAs) confirm that dimerization and sequence-specific IR recognition are essential for DNA binding. Despite mechanistic similarities, these and other Aca proteins exhibit notable differences. Structural comparisons across Aca families reveal that while monomer structures are generally similar with conserved HTH motifs, the structures of their dimeric functional units vary significantly. These structural differences might be essential for Aca proteins to bind to various promoters and regulate the expression of different Acr proteins.

Full Text

We can’t show the full text here under this license. Use the link below to read it at the source.

View full text (PDF) ↗View full text (HTML) ↗

Regulation of anti-CRISPR operons by structurally distinct families of Aca proteins

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the crispr gene editing brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the crispr gene editing brief