Details

Autor(en) / Beteiligte

• Hwang, Sungwon
• Pan, Chuxi
• Garcia, Bianca
• Davidson, Alan R.
• Moraes, Trevor F.
• Maxwell, Karen L.

Titel

Structural and Mechanistic Insight into CRISPR-Cas9 Inhibition by Anti-CRISPR Protein AcrIIC4Hpa

Ist Teil von

• Journal of molecular biology, 2022-03, Vol.434 (5), p.167420-167420, Article 167420

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• [Display omitted] •AcrIIC4Hpa inhibits DNA cleavage by the type II-C CRISPR-Cas system through an interaction with the REC2 domain.•The X-ray crystal structure of AcrIIC4Hpa reveals a dimeric helical bundle.•AcrIIC4Hpa provides a novel mechanism of inhibition of CRISPR-Cas activity. Phages, plasmids, and other mobile genetic elements express inhibitors of CRISPR-Cas immune systems, known as anti-CRISPR proteins, to protect themselves from targeted destruction. These anti-CRISPR proteins have been shown to function through very diverse mechanisms. In this work we investigate the activity of an anti-CRISPR isolated from a prophage in Haemophilus parainfluenzae that blocks CRISPR-Cas9 DNA cleavage activity. We determine the three-dimensional crystal structure of AcrIIC4Hpa and show that it binds to the Cas9 Recognition Domain. This binding does not prevent the Cas9-anti-CRISPR complex from interacting with target DNA but does inhibit DNA cleavage. AcrIIC4Hpa likely acts by blocking the conformational changes that allow the HNH and RuvC endonuclease domains to contact the DNA sites to be nicked.