Researchers Characterise an Anti-CRISPR Protein That Pulls Apart a CRISPR-Cas Complex

Researchers in Canada and China report the characterisation of AcrIF25, an anti-CRISPR protein that inhibits the type I-F CRISPR-Cas system by dismantling the fully assembled effector complex.

By: Karen O'Hanlon Cohrt - Jul. 4, 2024
News

Protein inhibitors play a crucial role in nature and have been exploited in biotech and medicine, to turn off the activities of enzymes and enzymatic complexes when they are no longer needed or when they contribute to disease.

Anti-CRISPR proteins that inhibit the activity of CRISPR-Cas systems are among the largest group of protein inhibitors described to date. Since the first discovery of acr genes in phages (in 2013), which encode protein inhibitors of the type I–F CRISPR–Cas system of Pseudomonas aeruginosa, more than 90 families of anti-CRISPR proteins with diverse mechanisms have been described.

In a study published in Nature yesterday, researchers in Canada and China report on the characterisation of one such anti-CRISPR protein, AcrIF25. The team, led by Alan Davidson at the University of Toronto, demonstrates that AcrIF25 inhibits the type I-F CRISPR-Cas system by pulling apart the fully assembled effector complex. They show that AcrIF25 binds the predominant CRISPR RNA-binding components of the effector complex, which is made up of six Cas7 subunits, and strips them from the RNA.

Through structural and biochemical studies, they find support for a model whereby AcrIF25 removes one Cas7 subunit at a time, starting at one end of the complex, and that this happens without any apparant enzymatic activity. They propose AcrIF25 as the first example of a protein that disassembles a large and stable macromolecular complex in the absence of an external energy source, and present AcrIF25 as a paradigm for macromolecular complex inhibitors with potential in biotech applications.

Read the full article in Nature here.

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