SNAP output for PDB entry 6wxy [SNAP web server]

PDB-id

6wxy; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein-RNA

Method

X-ray (2.1 Å)

Summary

Crystal structure of ca6-bound card1

Reference

Rostol JT, Xie W, Kuryavyi V, Maguin P, Kao K, Froom R, Patel DJ, Marraffini LA (2021): "The Card1 nuclease provides defence during type III CRISPR immunity." Nature, 590, 624-629. doi: 10.1038/s41586-021-03206-x.

Abstract

During the prokaryotic type III CRISPR-Cas immune response, infection triggers the production of cyclic oligoadenylates, which bind and activate CARF domain-containing proteins_1,2. Many type III loci are associated with proteins in which the CARF domain is fused to an endonuclease-like domain_3,4; however, with the exception of the well-characterized Csm6/Csx1 RNases_5,6, whether and how these inducible effectors provide defense is not known. Here we investigated one of such type III CRISPR accessory proteins, Card1. Card1 forms a symmetrical dimer with a large central cavity between its CARF and restriction endonuclease (REase) domains that binds cA₄. Ligand binding results in a conformational change where individual monomers rotate relative to each other to form a more compact dimeric scaffold wherein a Mn cation coordinates to the catalytic residues and activates the cleavage of single, but not double, stranded nucleic acids (DNA and RNA). In vivo, Card1 activation induces dormancy of the infected hosts to provide immunity against phage infection and plasmids. Our results highlight the diversity of strategies used by CRISPR systems to provide immunity.