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dc.contributor.author | Rivera Calzada, Angel | |
dc.contributor.author | Arribas-Bosacoma, Raquel | |
dc.contributor.author | Ruiz-Ramos, Alba | |
dc.contributor.author | Escudero-Bravo, Paloma | |
dc.contributor.author | Boskovic, Jasminka | |
dc.contributor.author | Fernandez-Leiro, Rafael | |
dc.contributor.author | Oliver, Antony W | |
dc.contributor.author | Pearl, Laurence H | |
dc.contributor.author | Llorca Blanco, Oscar Antonio | |
dc.date.accessioned | 2023-05-16T08:39:17Z | |
dc.date.available | 2023-05-16T08:39:17Z | |
dc.date.issued | 2022-11-18 | |
dc.identifier.citation | Nat Commun. 2022 ;13(1):7062. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/16060 | |
dc.description.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. | es_ES |
dc.description.sponsorship | We acknowledge the help of Dr Christos Savva from the Leicester Institute of Structural and Chemical Biology (UK) for assistance with data collection, and the help of Clara Santiveri and Ramon Campos from the Spectroscopy and Nuclear Magnetic Resonance Unit at CNIO for their assistance in the Mass Photometry experiments. We thank Tomas de Garay and REFEYN (Oxford, UK) for their assistance during mass photometry measurements. We acknowledge the support of the National Institute of Health Carlos III to CNIO. This work was funded by the Autonomous Region of Madrid and co-funded by the European Social Fund and the European Regional Development Fund [Y2018/BIO-4747 and P2018/NMT-4443 to O.L], and by Cancer Research UK Programme Grants C302/A14532 and C302/A24386, to A.W.O and L.H.P. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Vaccinia virus | es_ES |
dc.subject.mesh | DNA-Binding Proteins | es_ES |
dc.subject.mesh | Ku Autoantigen | es_ES |
dc.subject.mesh | DNA | es_ES |
dc.subject.mesh | DNA-Activated Protein Kinase | es_ES |
dc.title | Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 36400800 | es_ES |
dc.format.volume | 13 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 7062 | es_ES |
dc.identifier.doi | 10.1038/s41467-022-34843-z | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Social Europeo (ESF/FSE) | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea | es_ES |
dc.contributor.funder | Cancer Research UK (Reino Unido) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41467-022-34843-z. | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Complejos Macromoleculares en la Respuesta a Daños en el DNA | es_ES |
dc.repisalud.orgCNIO | CNIO::Unidades técnicas::Unidad de Microscopía Electrónica | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/P2018/NMT-4443 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/Y2018/BIO-4747 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement//P2018/NMT-4443 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/C302/A14532 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/C302/A24386 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFIS | / PI17/01865 | es_ES |