Crystal structure of the anti-CRISPR repressor Aca2

• Published in: Journal of structural biology 2021-09, Vol.213 (3), p.107752-107752, Article 107752
• Main Authors: Usher, Ben, Birkholz, Nils, Beck, Izaak N., Fagerlund, Robert D., Jackson, Simon A., Fineran, Peter C., Blower, Tim R.
• Format: Article
• Language: English
• Subjects: Aca2; Anti-CRISPR associated; CRISPR; Structure Report; Transcriptional regulator; X-ray crystallography
• ISSN: 1047-8477; 1095-8657
• DOI: 10.1016/j.jsb.2021.107752

[Display omitted] •The crystal structure of the anti-CRISPR repressor Aca2 has been solved to 1.34 Å.•Aca2 contains a new dimerization domain for HTH transcriptional regulators.•Aca2-like regulators are found encoded in diverse biological contexts. Bacteria use adaptive CRISPR-Cas immune mechanisms to protect from invasion by bacteriophages and other mobile genetic elements. In response, bacteriophages and mobile genetic elements have co-evolved anti-CRISPR proteins to inhibit the bacterial defense. We and others have previously shown that anti-CRISPR associated (Aca) proteins can regulate this anti-CRISPR counter-attack. Here, we report the first structure of an Aca protein, the Aca2 DNA-binding transcriptional autorepressor from Pectobacterium carotovorum bacteriophage ZF40, determined to 1.34 Å. Aca2 presents a conserved N-terminal helix-turn-helix DNA-binding domain and a previously uncharacterized C-terminal dimerization domain. Dimerization positions the Aca2 recognition helices for insertion into the major grooves of target DNA, supporting its role in regulating anti-CRISPRs. Furthermore, database comparisons identified uncharacterized Aca2 structural homologs in pathogenic bacteria, suggesting that Aca2 represents the first characterized member of a more widespread family of transcriptional regulators.