| Title |
Structural variation of types IV-A1- and IV-A3-mediated CRISPR interference / |
| Authors |
Čepaitė, Rimvydė ; Klein, Nathalie ; Mikšys, Algirdas ; Camara-Wilpert, Sarah ; Ragožius, Viktoras ; Benz, Fabienne ; Skorupskaitė, Aistė ; Becker, Hannah ; Steube, Niklas ; Hochberg, Georg ; Randau, Lennart ; Pinilla-Redondo, Rafael ; Malinauskaitė, Lina ; Pausch, Patrick |
| DOI |
10.1038/s41467-024-53778-1 |
| Full Text |
|
| Is Part of |
Nature communications.. Berlin : Nature Portfolio. 2024, vol. 15, art. no. 9306, p. [1-18].. eISSN 2041-1723 |
| Keywords [eng] |
CRISPR-Cas ; type IV-A ; DinG ; helicase ; DNA-interference ; cryo-EM |
| Abstract [eng] |
CRISPR-Cas mediated DNA-interference typically relies on sequence-specific binding and nucleolytic degradation of foreign genetic material. Type IV-A CRISPR-Cas systems diverge from this general mechanism, using a nuclease-independent interference pathway to suppress gene expression for gene regulation and plasmid competition. To understand how the type IV-A system associated effector complex achieves this interference, we determine cryo-EM structures of two evolutionarily distinct type IV-A complexes (types IV-A1 and IV-A3) bound to cognate DNA-targets in the presence and absence of the type IV-A signature DinG effector helicase. The structures reveal how the effector complexes recognize the protospacer adjacent motif and target-strand DNA to form an R-loop structure. Additionally, we reveal differences between types IV-A1 and IV-A3 in DNA interactions and structural motifs that allow for in trans recruitment of DinG. Our study provides a detailed view of type IV-A mediated DNA-interference and presents a structural foundation for engineering type IV-A-based genome editing tools. |
| Published |
Berlin : Nature Portfolio |
| Type |
Journal article |
| Language |
English |
| Publication date |
2024 |
| CC license |
|
