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-Structure paper
Title | Structural determinants of DNA cleavage by a CRISPR HNH-Cascade system. |
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Journal, issue, pages | Mol Cell, Vol. 84, Issue 16, Page 3154-33162.e5, Year 2024 |
Publish date | Aug 22, 2024 |
Authors | Seiichi Hirano / Han Altae-Tran / Soumya Kannan / Rhiannon K Macrae / Feng Zhang / |
PubMed Abstract | Canonical prokaryotic type I CRISPR-Cas adaptive immune systems contain a multicomponent effector complex called Cascade, which degrades large stretches of DNA via Cas3 helicase-nuclease activity. ...Canonical prokaryotic type I CRISPR-Cas adaptive immune systems contain a multicomponent effector complex called Cascade, which degrades large stretches of DNA via Cas3 helicase-nuclease activity. Recently, a highly precise subtype I-F1 CRISPR-Cas system (HNH-Cascade) was found that lacks Cas3, the absence of which is compensated for by the insertion of an HNH endonuclease domain in the Cas8 Cascade component. Here, we describe the cryo-EM structure of Selenomonas sp. HNH-Cascade (SsCascade) in complex with target DNA and characterize its mechanism of action. The Cascade scaffold is complemented by the HNH domain, creating a ring-like structure in which the unwound target DNA is precisely cleaved. This structure visualizes a unique hybrid of two extensible biological systems-Cascade, an evolutionary platform for programmable DNA effectors, and an HNH nuclease, an adaptive domain with a spectrum of enzymatic activity. |
External links | Mol Cell / PubMed:39111310 |
Methods | EM (single particle) |
Resolution | 3.5 Å |
Structure data | EMDB-43729, PDB-8w1p: |
Source |
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Keywords | IMMUNE SYSTEM / CRISPR-Cas / Genome engineering / RNA-guided DNA endonuclease / Non-coding RNA / HNH nuclease |