2026-08-29T14:07:57Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/160602024-11-29T17:55:49Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2022-11-18 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. 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 Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.