Structural highlights
Publication Abstract from PubMed
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.
Structural snapshots of R-loop formation by a type I-C CRISPR Cascade.,O'Brien RE, Bravo JPK, Ramos D, Hibshman GN, Wright JT, Taylor DW Mol Cell. 2023 Mar 2;83(5):746-758.e5. doi: 10.1016/j.molcel.2023.01.024. Epub , 2023 Feb 16. PMID:36805026[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ O'Brien RE, Bravo JPK, Ramos D, Hibshman GN, Wright JT, Taylor DW. Structural snapshots of R-loop formation by a type I-C CRISPR Cascade. Mol Cell. 2023 Mar 2;83(5):746-758.e5. PMID:36805026 doi:10.1016/j.molcel.2023.01.024
