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Structural snapshots of R-loop formation by a type I-C CRISPR Cascade.
O'Brien, Roisin E; Bravo, Jack P K; Ramos, Delisa; Hibshman, Grace N; Wright, Jacquelyn T; Taylor, David W.
Affiliation
  • O'Brien RE; Interdisciplinary Life Sciences Graduate Programs, University of Texas at Austin, Austin, TX 78712, USA.
  • Bravo JPK; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
  • Ramos D; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
  • Hibshman GN; Interdisciplinary Life Sciences Graduate Programs, University of Texas at Austin, Austin, TX 78712, USA.
  • Wright JT; Interdisciplinary Life Sciences Graduate Programs, University of Texas at Austin, Austin, TX 78712, USA.
  • Taylor DW; Interdisciplinary Life Sciences Graduate Programs, University of Texas at Austin, Austin, TX 78712, USA; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA; Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA; LIVESTRO
Mol Cell ; 83(5): 746-758.e5, 2023 03 02.
Article in En | MEDLINE | ID: mdl-36805026
Type I CRISPR-Cas systems employ multi-subunit Cascade effector complexes to target foreign nucleic acids for destruction. Here, we present structures of D. vulgaris type I-C Cascade at various stages of double-stranded (ds)DNA target capture, revealing mechanisms that underpin PAM recognition and Cascade allosteric activation. We uncover an interesting mechanism of non-target strand (NTS) DNA stabilization via stacking interactions with the "belly" subunits, securing the NTS in place. This "molecular seatbelt" mechanism facilitates efficient R-loop formation and prevents dsDNA reannealing. Additionally, we provide structural insights into how two anti-CRISPR (Acr) proteins utilize distinct strategies to achieve a shared mechanism of type I-C Cascade inhibition by blocking PAM scanning. These observations form a structural basis for directional R-loop formation and reveal how different Acr proteins have converged upon common molecular mechanisms to efficiently shut down CRISPR immunity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: CRISPR-Associated Proteins / R-Loop Structures Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2023 Document type: Article Affiliation country: United States Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: CRISPR-Associated Proteins / R-Loop Structures Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2023 Document type: Article Affiliation country: United States Country of publication: United States