2026-05-21T23:07:24Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/160602024-11-29T17:55:49Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Rivera Calzada, Angel
author
Arribas-Bosacoma, Raquel
author
Ruiz-Ramos, Alba
author
Escudero-Bravo, Paloma
author
Boskovic, Jasminka
author
Fernandez-Leiro, Rafael
author
Oliver, Antony W
author
Pearl, Laurence H
author
Llorca Blanco, Oscar Antonio
author
Arribas-Bosacoma, Raquel
author
Ruiz-Ramos, Alba
author
Escudero-Bravo, Paloma
author
Fernandez-Leiro, Rafael
author
Oliver, Antony W
author
Pearl, Laurence H
funder
Instituto de Salud Carlos III
funder
Comunidad de Madrid (España)
funder
Unión Europea. Fondo Social Europeo (ESF/FSE)
funder
Unión Europea. Comisión Europea
funder
Cancer Research UK (Reino Unido)
2023-05-16T08:39:17Z
2023-05-16T08:39:17Z
2022-11-18
Nat Commun. 2022 ;13(1):7062.
10.1038/s41467-022-34843-z
2041-1723
Nature communications
36400800
http://hdl.handle.net/20.500.12105/16060
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.
eng
Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.
journal article
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