7F45

Structure of an Anti-CRISPR protein

Summary for 7F45

• Entry DOI: 10.2210/pdb7f45/pdb
• Descriptor: AcrIF5 (1 entity in total)
• Functional Keywords: monomer, mixed alpha-beta structure, immune system
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 2
• Total formula weight: 17063.73

Authors

Feng, Y. (deposition date: 2021-06-17, release date: 2022-03-09, Last modification date: 2023-11-29)

Primary citation

Xie, Y.,Zhang, L.,Gao, Z.,Yin, P.,Wang, H.,Li, H.,Chen, Z.,Zhang, Y.,Yang, M.,Feng, Y.
AcrIF5 specifically targets DNA-bound CRISPR-Cas surveillance complex for inhibition.
Nat.Chem.Biol., 18:670-677, 2022

PubMed Abstract: CRISPR-Cas systems are prokaryotic antiviral systems, and phages use anti-CRISPR proteins (Acrs) to inactivate these systems. Here we present structural and functional analyses of AcrIF5, exploring its unique anti-CRISPR mechanism. AcrIF5 shows binding specificity only for the target DNA-bound form of the crRNA-guided surveillance (Csy) complex, but not the apo Csy complex from the type I-F CRISPR-Cas system. We solved the structure of the Csy-dsDNA-AcrIF5 complex, revealing that the conformational changes of the Csy complex caused by dsDNA binding dictate the binding specificity for the Csy-dsDNA complex by AcrIF5. Mechanistically, five AcrIF5 molecules bind one Csy-dsDNA complex, which destabilizes the helical bundle domain of Cas8f, thus preventing subsequent Cas2/3 recruitment. AcrIF5 exists in symbiosis with AcrIF3, which blocks Cas2/3 recruitment. This attack on the recruitment event stands in contrast to the conventional mechanisms of blocking binding of target DNA. Overall, our study reveals an unprecedented mechanism of CRISPR-Cas inhibition by AcrIF5.

PubMed: 35301482
DOI: 10.1038/s41589-022-00995-8

Experimental method

X-RAY DIFFRACTION (3.52 Å)