ArticleNucleic acids research2020
Intrinsic disorder is essential for Cas9 inhibition of anti-CRISPR AcrIIA5.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Research on Prophages in Aquaculture from the Perspective of Paradigm Borrowing: Advances in Pathogen Virulence, Antimicrobial Resistance, and Environmental Regulation.Microorganisms · 2026Review
- Optimized optogenetic anti-CRISPR for endogenous gene regulation in Drosophila.Nucleic acids research · 2026Article
- Defense Systems and Prophage Detection in Streptococcus mutans Strains.Molecular oral microbiology · 2026Article
- CRISPR-anti-CRISPR dynamics: evolutionary, ecological and biotechnological perspectives.Archives of microbiology · 2026Review
- Anti-CRISPR protein AcrIIA5 can enhance the activity and security of prime editing.Nature communications · 2025Article
- Article
- CRISPR/Cas9 Ribonucleoprotein Delivery Enhanced by Lipo-Xenopeptide Carriers and Homology-Directed Repair Modulators: Insights from Reporter Cell Lines.International journal of molecular sciences · 2025Article
- Mechanism of Cas9 inhibition by AcrIIA11.Nucleic acids research · 2025Article
- A deep mutational scanning platform to characterize the fitness landscape of anti-CRISPR proteins.Nucleic acids research · 2024Article
- SpCas9-HF1 enhances accuracy of cell cycle-dependent genome editing by increasing HDR efficiency, and by reducing off-target effects and indel rates.Molecular therapy. Nucleic acids · 2024Article
- The Many (Inter)faces of Anti-CRISPRs: Modulation of CRISPR-Cas Structure and Dynamics by Mechanistically Diverse Inhibitors.Biomolecules · 2023Review
- Discovery of potent and versatile CRISPR-Cas9 inhibitors engineered for chemically controllable genome editing.Nucleic acids research · 2022Article
- Investigating the disordered regions (MoRFs, SLiMs and LCRs) and functions of mimicry proteins/peptides in silico.PloS one · 2022Article
- Novel Virulent Bacteriophage ΦSG005, Which InfectsViruses · 2021Article
- Structure-based functional mechanisms and biotechnology applications of anti-CRISPR proteins.Nature reviews. Molecular cell biology · 2021Review
- Type II anti-CRISPR proteins as a new tool for synthetic biology.RNA biology · 2021Review
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins provide adaptive immunity to prokaryotes against invading phages and plasmids. As a countermeasure, phages have evolved anti-CRISPR (Acr) proteins that neutralize the CRISPR immunity. AcrIIA5, isolated from a virulent phage of Streptococcus thermophilus, strongly inhibits diverse Cas9 homologs, but the molecular mechanism underlying the Cas9 inhibition remains unknown. Here, we report the solution structure of AcrIIA5, which features a novel α/β fold connected to an N-terminal intrinsically disordered region (IDR). Remarkably, truncation of the N-terminal IDR abrogates the inhibitory activity against Cas9, revealing that the IDR is essential for Cas9 inhibition by AcrIIA5. Progressive truncations and mutations of the IDR illustrate that the disordered region not only modulates the association between AcrIIA5 and Cas9-sgRNA, but also alters the catalytic efficiency of the inhibitory complex. The length of IDR is critical for the Cas9-sgRNA recognition by AcrIIA5, whereas the charge content of IDR dictates the inhibitory activity. Conformational plasticity of IDR may be linked to the broad-spectrum inhibition of Cas9 homologs by AcrIIA5. Identification of the IDR as the main determinant for Cas9 inhibition expands the inventory of phage anti-CRISPR mechanisms.
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