ArticleNucleic acids research2022
Allosteric activation of CRISPR-Cas12a requires the concerted movement of the bridge helix and helix 1 of the RuvC II domain.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Size and sequence variation of the Lid of the Cas12a nuclease domain results in a nickase phenotype.Nucleic acids research · 2026Article
- Helicity of the bridge helix of Cas12a regulates on-target DNA cleavage efficiency and off-target cleavage propensity.Biochemical and biophysical research communications · 2026Article
- Bridge helix of Cas12a is an allosteric regulator of R-loop formation and RuvC activation.Nature communications · 2026Article
- Nuc domain electrostatics drive the trans cleavage activity of CRISPR-Cas12a.Nucleic acids research · 2026Article
- A resurrected ancestor of Cas12a expands target access and substrate recognition for nucleic acid editing and detection.Nature biotechnology · 2025Article
- Enhanced One-Pot Cas12a-Based Nucleic Acid Detection via Epitope Insertion and Recruitment of Rad51.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- And… cut! - how conformational regulation of CRISPR-Cas effectors directs nuclease activity.The Biochemical journal · 2025Review
- CRISPR-Cas12a REC2-Nuc interactions drive target-strand cleavage and constrain trans cleavage.Nucleic acids research · 2025Article
- Unleashing high trans-substrate cleavage kinetics of Cas12a for nucleic acid diagnostics.Nucleic acids research · 2025Article
- Cas12a domain flexibility guides R-loop formation and forces RuvC resetting.Molecular cell · 2024Article
- Intrinsic RNA Targeting Triggers Indiscriminate DNase Activity of CRISPR-Cas12a.Angewandte Chemie (International ed. in English) · 2024Article
- An alpha-helical lid guides the target DNA toward catalysis in CRISPR-Cas12a.Nature communications · 2024Article
- Current Updates of CRISPR/Cas System and Anti-CRISPR Proteins: Innovative Applications to Improve the Genome Editing Strategies.International journal of nanomedicine · 2024Review
- A DNA unwinding equilibrium serves as a checkpoint for CRISPR-Cas12a target discrimination.Nucleic acids research · 2023Article
- Improved genome editing by an engineered CRISPR-Cas12a.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleases derived from the prokaryotic defense system CRISPR-Cas are frequently re-purposed for gene editing and molecular diagnostics. Hence, an in-depth understanding of the molecular mechanisms of these enzymes is of crucial importance. We focused on Cas12a from Francisella novicida (FnCas12a) and investigated the functional role of helix 1, a structural element that together with the bridge helix (BH) connects the recognition and the nuclease lobes of FnCas12a. Helix 1 is structurally connected to the lid domain that opens upon DNA target loading thereby activating the active site of FnCas12a. We probed the structural states of FnCas12a variants altered in helix 1 and/or the bridge helix using single-molecule FRET measurements and assayed the pre-crRNA processing, cis- and trans-DNA cleavage activity. We show that helix 1 and not the bridge helix is the predominant structural element that confers conformational stability of FnCas12a. Even small perturbations in helix 1 lead to a decrease in DNA cleavage activity while the structural integrity is not affected. Our data, therefore, implicate that the concerted remodeling of helix 1 and the bridge helix upon DNA binding is structurally linked to the opening of the lid and therefore involved in the allosteric activation of the active site.
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