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TitleStructural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 7062, Year 2022
Publish dateNov 18, 2022
AuthorsAngel Rivera-Calzada / Raquel Arribas-Bosacoma / Alba Ruiz-Ramos / Paloma Escudero-Bravo / Jasminka Boskovic / Rafael Fernandez-Leiro / Antony W Oliver / Laurence H Pearl / Oscar Llorca /
PubMed AbstractDetection 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 ...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.
External linksNat Commun / PubMed:36400800 / PubMed Central
MethodsEM (single particle)
Resolution2.46 - 3.47 Å
Structure data

15414

8ag3

EMDB-15414, PDB-8ag3:
Vaccinia C16 N-terminal domains
Method: EM (single particle) / Resolution: 3.47 Å

15415

8ag4

EMDB-15415, PDB-8ag4:
Vaccinia C16 protein bound to Ku70/Ku80
Method: EM (single particle) / Resolution: 2.46 Å

15416

8ag5

EMDB-15416, PDB-8ag5:
Vaccinia C16 protein bound to Ku70/Ku80
Method: EM (single particle) / Resolution: 3.47 Å

Source
  • Vaccinia virus
  • vaccinia virus western reserve
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / C16 vaccinia virus protein Ku70/Ku80 DNA binding inhibition

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