VU LSC-EMBL Partnership

Introduction Obesity is a growing health issue for the human population worldwide (World Health Organization, 2021). Due to the consumption of high-fat diet (HFD) and Western-type diet (Ahima, 2011), the number of overweight and obese adults has exceeded more than 1.9 billion in 2017–2018, representing 42.5% of the United States population (Fryar et al., 2020), 64% of Canada population (Government Of Canada, 2018), and 53% of the European population (EUROSTAT, 2021).

Abstract CRISPR–CasΦ, a small RNA-guided enzyme found uniquely in bacteriophages, achieves programmable DNA cutting as well as genome editing. To investigate how the hypercompact enzyme recognizes and cleaves double-stranded DNA, we determined cryo-EM structures of CasΦ (Cas12j) in pre- and post-DNA-binding states. The structures reveal a streamlined protein architecture that tightly encircles the CRISPR RNA and DNA target to capture, unwind and cleave DNA.