Crystal structure of Cmr2 suggests a nucleotide cyclase-related enzyme in type III CRISPR-Cas systems

CRISPR RNAs (crRNAs) mediate sequence-specific silencing of invading viruses and plasmids in prokaryotes. The crRNA–Cmr protein complex cleaves complementary RNA. We report the crystal structure of Pyrococcus furiosus Cmr2 (Cas10), a component of this Cmr complex and the signature protein in type III CRISPR systems. The structure reveals a nucleotide cyclase domain with a set of conserved catalytic residues that associates with an unexpected deviant cyclase domain like dimeric cyclases. Additionally, two helical domains resemble the thumb domain of A-family DNA polymerase and Cmr5, respectively. Our results suggest that Cmr2 possesses novel enzymatic activity that remains to be elucidated.

► The crystal structure of CRISPR-associated protein Cmr2 was determined. ► Cmr2 is a structural homolog of adenylate cyclase dimer with a putative active site. ► Cmr2 also contains a polymerase thumb-like domain and a Cmr5-like domain. ► Cmr2 is likely an enzyme with novel activity on nucleotides or nucleic acids.