ArticleNature structural & molecular biology2023
Mechanistic and evolutionary insights into a type V-M CRISPR-Cas effector enzyme.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Structure-guided discovery and engineering of miniature CRISPR-Cas12m for epigenome editing.Nature structural & molecular biology · 2026Article
- Research Progress in Applications of the CRISPR-Cas12b System in Pathogen Nucleic Acid Detection.Current issues in molecular biology · 2026Review
- Cas-regulation-targeting chimera enables selective and tunable control of CRISPR/Cas12a.Nucleic acids research · 2026Article
- Precise, specific gene editing via a compact GoCas12m-FokI chimeric nuclease.Nucleic acids research · 2026Article
- On-Column Dual-Gradient Refolding for Efficient Recovery of Insoluble Affinity-Tagged Recombinant Proteins.Bio-protocol · 2026Article
- Structural visualization of the molecular evolution of CRISPR-Cas9.Nature structural & molecular biology · 2026Article
- Phage-associated Cas12p nucleases require binding to bacterial thioredoxin for activation and cleavage of target DNA.Nature microbiology · 2026Article
- Mechanisms and engineering of a miniature type V-N CRISPR-Cas12 effector enzyme.Nature communications · 2025Article
- Structural basis for target DNA cleavage and guide RNA processing by CRISPR-Casλ2.Communications biology · 2025Article
- Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025Review
- Emerging tools in plant genome editing.Frontiers in genome editing · 2025Review
- AAV-mediated gene therapies by miniature gene editing tools.Science China. Life sciences · 2024Review
- Discovering CRISPR-Cas system with self-processing pre-crRNA capability by foundation models.Nature communications · 2024Article
- Structural determinants of DNA cleavage by a CRISPR HNH-Cascade system.Molecular cell · 2024Article
- Cas12a domain flexibility guides R-loop formation and forces RuvC resetting.Molecular cell · 2024Article
- Advances in miniature CRISPR-Cas proteins and their applications in gene editing.Archives of microbiology · 2024Review
- Innate programmable DNA binding by CRISPR-Cas12m effectors enable efficient base editing.Nucleic acids research · 2024Article
- Recent application of CRISPR-Cas12 and OMEGA system for genome editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Recent advances in genome engineering by CRISPR technology.BMB reports · 2024Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA-guided type V CRISPR-Cas12 effectors provide adaptive immunity against mobile genetic elements (MGEs) in bacteria and archaea. Among diverse Cas12 enzymes, the recently identified Cas12m2 (CRISPR-Cas type V-M) is highly compact and has a unique RuvC active site. Although the non-canonical RuvC triad does not permit dsDNA cleavage, Cas12m2 still protects against invading MGEs through transcriptional silencing by strong DNA binding. However, the molecular mechanism of RNA-guided genome inactivation by Cas12m2 remains unknown. Here we report cryo-electron microscopy structures of two states of Cas12m2-CRISPR RNA (crRNA)-target DNA ternary complexes and the Cas12m2-crRNA binary complex, revealing structural dynamics during crRNA-target DNA heteroduplex formation. The structures indicate that the non-target DNA strand is tightly bound to a unique arginine-rich cluster in the recognition (REC) domains and the non-canonical active site in the RuvC domain, ensuring strong DNA-binding affinity of Cas12m2. Furthermore, a structural comparison of Cas12m2 with TnpB, a putative ancestor of Cas12 enzymes, suggests that the interaction of the characteristic coiled-coil REC2 insertion with the protospacer-adjacent motif-distal region of the heteroduplex is crucial for Cas12m2 to engage in adaptive immunity. Collectively, our findings improve mechanistic understanding of diverse type V CRISPR-Cas effectors and provide insights into the evolution of TnpB to Cas12 enzymes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.