Crystal structure of the anti-CRISPR repressor Aca2

Usher, B.; Birkholz, N.; Beck, I.N.; Fagerlund, R.D.; Jackson, S.A.; Fineran, P.C.; Blower, T.R.

Abstract

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.

Citation

Usher, B., Birkholz, N., Beck, I., Fagerlund, R., Jackson, S., Fineran, P., & Blower, T. (2021). Crystal structure of the anti-CRISPR repressor Aca2. Journal of Structural Biology, 213(3), Article 107752. https://doi.org/10.1016/j.jsb.2021.107752

• Journal Article Type: Article
• Acceptance Date: Jun 6, 2021
• Online Publication Date: Jun 8, 2021
• Publication Date: 2021-09
• Deposit Date: Jun 7, 2021
• Publicly Available Date: Jun 24, 2021
• Journal: Journal of Structural Biology
• Print ISSN: 1047-8477
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 213
• Issue: 3
• Article Number: 107752
• DOI: https://doi.org/10.1016/j.jsb.2021.107752
• Public URL: https://durham-repository.worktribe.com/output/1247345