SNAP output for PDB entry 6sh8 [SNAP web server]

PDB-id

6sh8; SNAP-derived features in text and JSON formats; DNAproDB

Class

antiviral protein

Method

cryo-EM (3.14 Å)

Summary

cryo-EM structure of the type iii-b cmr-beta bound to cognate target RNA and amppnp, state 2, in the presence of ssDNA

Reference

Sofos N, Feng M, Stella S, Pape T, Fuglsang A, Lin J, Huang Q, Li Y, She Q, Montoya G (2020): "Structures of the Cmr-beta Complex Reveal the Regulation of the Immunity Mechanism of Type III-B CRISPR-Cas." Mol.Cell, 79, 741-757.e7. doi: 10.1016/j.molcel.2020.07.008.

Abstract

Cmr-β is a type III-B CRISPR-Cas complex that, upon target RNA recognition, unleashes a multifaceted immune response against invading genetic elements, including single-stranded DNA (ssDNA) cleavage, cyclic oligoadenylate synthesis, and also a unique UA-specific single-stranded RNA (ssRNA) hydrolysis by the Cmr2 subunit. Here, we present the structure-function relationship of Cmr-β, unveiling how binding of the target RNA regulates the Cmr2 activities. Cryoelectron microscopy (cryo-EM) analysis revealed the unique subunit architecture of Cmr-β and captured the complex in different conformational stages of the immune response, including the non-cognate and cognate target-RNA-bound complexes. The binding of the target RNA induces a conformational change of Cmr2, which together with the complementation between the 5' tag in the CRISPR RNAs (crRNA) and the 3' antitag of the target RNA activate different configurations in a unique loop of the Cmr3 subunit, which acts as an allosteric sensor signaling the self- versus non-self-recognition. These findings highlight the diverse defense strategies of type III complexes.