A hypercompact Type I-F2 CRISPR-Cas system

Perry, T.N., Mais, C.-N., Sanchez-Londono, M., Steinchen, W., Plitzko, P.A., Randau, L., Pausch, P., Innis, C.A., Bange, G. (2026). Structural basis of Cas8-independent Cas3 recruitment in Type I-F2 CRISPR-Cas. Nucleic Acids Res., 54, gkag136.

In this collaborative study with the Bange and Pausch groups, we report the cryo-EM structure of the hypercompact Type I-F2 CRISPR–Cas complex bound to its DNA target and the nuclease-helicase Cas3, revealing how this streamlined system operates without the canonical large (Cas8) and small (Cas11) subunits. We show that Cas5 alone performs PAM recognition, while Cas7 subunits directly recruit Cas3, which adopts a helicase-ready conformation to unwind and degrade invading DNA. By capturing the displaced DNA strand and initiating directional destruction, the I-F2 machinery achieves efficient interference through previously unknown structural adaptations. These findings highlight the remarkable mechanistic diversity within CRISPR systems and provide a structural blueprint for engineering this minimal, highly compact platform for genome editing and biotechnology applications.