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TitleStructural insights into the assembly and mechanism of mpox virus DNA polymerase complex F8-A22-E4-H5.
Journal, issue, pagesMol Cell, Vol. 83, Issue 23, Page 4398-44412.e4, Year 2023
Publish dateDec 7, 2023
AuthorsXiaohan Wang / Liangwen Ma / Ningning Li / Ning Gao /
PubMed AbstractThe DNA replication of mpox virus is performed by the viral polymerase F8 and also requires other viral factors, including processivity factor A22, uracil DNA glycosylase E4, and phosphoprotein H5. ...The DNA replication of mpox virus is performed by the viral polymerase F8 and also requires other viral factors, including processivity factor A22, uracil DNA glycosylase E4, and phosphoprotein H5. However, the molecular roles of these viral factors remain unclear. Here, we characterize the structures of F8-A22-E4 and F8-A22-E4-H5 complexes in the presence of different primer-template DNA substrates. E4 is located upstream of F8 on the template single-stranded DNA (ssDNA) and is catalytically active, highlighting a functional coupling between DNA base-excision repair and DNA synthesis. Moreover, H5, in the form of tetramer, binds to the double-stranded DNA (dsDNA) region downstream of F8 in a similar position as PCNA (proliferating cell nuclear antigen) does in eukaryotic polymerase complexes. Omission of H5 or disruption of its DNA interaction showed a reduced synthesis of full-length DNA products. These structures provide snapshots for the working cycle of the polymerase and generate insights into the mechanisms of these essential factors in viral DNA replication.
External linksMol Cell / PubMed:37995690
MethodsEM (single particle)
Resolution2.7 - 3.6 Å
Structure data

37714

8wpe

EMDB-37714, PDB-8wpe:
Structure of monkeypox virus polymerase complex F8-A22-E4-H5 (tag-free A22) with exogenous DNA
Method: EM (single particle) / Resolution: 2.7 Å

37715

8wpf

EMDB-37715, PDB-8wpf:
Structure of monkeypox virus polymerase complex F8-A22-E4-H5 with exogenous DNA bearing one abasic site
Method: EM (single particle) / Resolution: 3.0 Å

37717

8wpk

EMDB-37717, PDB-8wpk:
Structure of monkeypox virus polymerase complex F8-A22-E4-H5 with exgenous DNA
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-37721: Structure of monkeypox virus polymerase complex F8-A22-E4-H5 with exogenous DNA bearing one abasic site, the region of H5 optimized
Method: EM (single particle) / Resolution: 3.6 Å

37722

8wpp

EMDB-37722, PDB-8wpp:
Structure of monkeypox virus polymerase complex F8-A22-E4-H5 with endogenous DNA
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-D3T:
2',3'-DIDEOXY-THYMIDINE-5'-TRIPHOSPHATE

ChemComp-MG:
Unknown entry

Source
  • monkeypox virus
  • synthetic construct (others)
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / Viral DNA replication / monkeypox virus / polymerase / H5

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