8AG3

Vaccinia C16 N-terminal domains

Summary for 8AG3

• Entry DOI: 10.2210/pdb8ag3/pdb
• EMDB information: 15414 15415 15416
• Descriptor: Protein C10 (1 entity in total)
• Functional Keywords: c16 vaccinia virus protein ku70/ku80 dna binding inhibition, viral protein
• Biological source: Vaccinia virus Western Reserve
• Total number of polymer chains: 2
• Total formula weight: 84953.36

Authors

Rivera-Calzada, A.,Arribas-Bosacoma, R.,Pearl, L.H.,Llorca, O. (deposition date: 2022-07-19, release date: 2022-11-09, Last modification date: 2024-07-24)

Primary citation

Rivera-Calzada, A.,Arribas-Bosacoma, R.,Ruiz-Ramos, A.,Escudero-Bravo, P.,Boskovic, J.,Fernandez-Leiro, R.,Oliver, A.W.,Pearl, L.H.,Llorca, O.
Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.
Nat Commun, 13:7062-7062, 2022

PubMed Abstract: 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.

PubMed: 36400800
DOI: 10.1038/s41467-022-34843-z

Experimental method

ELECTRON MICROSCOPY (3.47 Å)