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TitleCryo-EM structure of DNA polymerase of African swine fever virus.
Journal, issue, pagesNucleic Acids Res, Vol. 52, Issue 17, Page 10717-10729, Year 2024
Publish dateSep 23, 2024
AuthorsLu Kuai / Junqing Sun / Qi Peng / Xuejin Zhao / Bin Yuan / Sheng Liu / Yuhai Bi / Yi Shi /
PubMed AbstractAfrican swine fever virus (ASFV) is one of the most important causative agents of animal diseases and can cause highly fatal diseases in swine. ASFV DNA polymerase (DNAPol) is responsible for genome ...African swine fever virus (ASFV) is one of the most important causative agents of animal diseases and can cause highly fatal diseases in swine. ASFV DNA polymerase (DNAPol) is responsible for genome replication and highly conserved in all viral genotypes showing an ideal target for drug development. Here, we systematically determined the structures of ASFV DNAPol in apo, replicating and editing states. Structural analysis revealed that ASFV DNAPol had a classical right-handed structure and showed the highest similarity to the structure of human polymerase delta. Intriguingly, ASFV DNAPol has a much longer fingers subdomain, and the thumb and palm subdomain form a unique interaction that has never been seen. Mutagenesis work revealed that the loss of this unique interaction decreased the enzymatic activity. We also found that the β-hairpin of ASFV DNAPol is located below the template strand in the editing state, which is different from the editing structures of other known B family DNAPols with the β-hairpin above the template strand. It suggests that B family DNAPols have evolved two ways to facilitate the dsDNA unwinding during the transition from replicating into editing state. These findings figured out the working mechanism of ASFV DNAPol and will provide a critical structural basis for the development of antiviral drugs.
External linksNucleic Acids Res / PubMed:39189451 / PubMed Central
MethodsEM (single particle)
Resolution2.7 - 3.28 Å
Structure data

EMDB-39632, PDB-8ywg:
The structure of ASFV DNA polymerase in apo state
Method: EM (single particle) / Resolution: 3.28 Å

EMDB-39634, PDB-8ywi:
The structure of ASFV DNA polymerase in replicating state
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-39638, PDB-8ywm:
The structure of ASFV DNA polymerase in editing state
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-TTP:
THYMIDINE-5'-TRIPHOSPHATE

Source
  • african swine fever virus
KeywordsVIRAL PROTEIN / DNA polymerase / VIRAL PROTEIN/DNA / VIRAL PROTEIN-DNA complex

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