Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.
Date
2022-11-18ICR Author
Author
Rivera-Calzada, A
Arribas-Bosacoma, R
Ruiz-Ramos, A
Escudero-Bravo, P
Boskovic, J
Fernandez-Leiro, R
Oliver, AW
Pearl, LH
Llorca, O
Type
Journal Article
Metadata
Show full item recordAbstract
Detection of cytosolic DNA is a central element of the innate immunity system against viral infection. The Ku heterodimer, a component of the NHEJ pathway of DNA repair in the nucleus, functions as DNA sensor that detects dsDNA of viruses that replicate in the cytoplasm. Vaccinia virus expresses two proteins, C4 and C16, that inactivate DNA sensing and enhance virulence. The structural basis for this is unknown. Here we determine the structure of the C16 - Ku complex using cryoEM. Ku binds dsDNA by a preformed ring but C16 sterically blocks this access route, abrogating binding to a dsDNA end and its insertion into DNA-PK, thereby averting signalling into the downstream innate immunity system. C4 replicates these activities using a domain with 54% identity to C16. Our results reveal how vaccinia virus subverts the capacity of Ku to recognize viral DNA.
Collections
Subject
Vaccinia virus
DNA-Binding Proteins
Ku Autoantigen
DNA
DNA-Activated Protein Kinase
Research team
Directorate Struct Biol
Language
eng
Date accepted
2022-11-08
License start date
2022-11-18
Citation
Nature Communications, 2022, 13 (1), pp. 7062 -
Publisher
NATURE PORTFOLIO