SNAP annotations: PDB entry 6ifz

PDB-id

6ifz; DSSR-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein

Method

cryo-EM (3.58 Å)

Summary

Type iii-a csm complex, cryo-EM structure of csm-ctr2-ssDNA complex

Reference

You L, Ma J, Wang J, Artamonova D, Wang M, Liu L, Xiang H, Severinov K, Zhang X, Wang Y (2019): "Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference." Cell, 176, 239-253.e16. doi: 10.1016/j.cell.2018.10.052.

Abstract

Csm, a type III-A CRISPR-Cas interference complex, is a CRISPR RNA (crRNA)-guided RNase that also possesses target RNA-dependent DNase and cyclic oligoadenylate (cOA) synthetase activities. However, the structural features allowing target RNA-binding-dependent activation of DNA cleavage and cOA generation remain unknown. Here, we report the structure of Csm in complex with crRNA together with structures of cognate or non-cognate target RNA bound Csm complexes. We show that depending on complementarity with the 5' tag of crRNA, the 3' anti-tag region of target RNA binds at two distinct sites of the Csm complex. Importantly, the interaction between the non-complementary anti-tag region of cognate target RNA and Csm1 induces a conformational change at the Csm1 subunit that allosterically activates DNA cleavage and cOA generation. Together, our structural studies provide crucial insights into the mechanistic processes required for crRNA-meditated sequence-specific RNA cleavage, RNA target-dependent non-specific DNA cleavage, and cOA generation.