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Structure paper

TitleEssential and multifunctional mpox virus E5 helicase-primase in double and single hexamer.
Journal, issue, pagesSci Adv, Vol. 10, Issue 34, Page eadl1150, Year 2024
Publish dateAug 23, 2024
AuthorsYunxia Xu / Yaqi Wu / Yuanyuan Zhang / Kaiting Gao / Xiaoying Wu / Yaxue Yang / Danyang Li / Biao Yang / Zhengyu Zhang / Changjiang Dong /
PubMed AbstractAn outbreak of mpox virus in May 2022 has spread over 110 nonpandemic regions in the world, posing a great threat to global health. Mpox virus E5, a helicase-primase, plays an essential role in DNA ...An outbreak of mpox virus in May 2022 has spread over 110 nonpandemic regions in the world, posing a great threat to global health. Mpox virus E5, a helicase-primase, plays an essential role in DNA replication, but the molecular mechanisms are elusive. Here, we report seven structures of mpox virus E5 in a double hexamer (DH) and six in single hexamer in different conformations, indicating a rotation mechanism for helicase and a coupling action for primase. The DH is formed through the interface of zinc-binding domains, and the central channel density indicates potential double-stranded DNA (dsDNA), which helps to identify dsDNA binding residues Arg, Lys, Lys, and Lys. Our work is important not only for understanding poxviral DNA replication but also for the development of novel therapeutics for serious poxviral infections including smallpox virus and mpox virus.
External linksSci Adv / PubMed:39167653 / PubMed Central
MethodsEM (single particle)
Resolution2.51 - 3.27 Å
Structure data

37522

8wgy

EMDB-37522, PDB-8wgy:
MPOX E5 hexamer AMP-PNP and ssDNA bound form with clear primase domain
Method: EM (single particle) / Resolution: 2.91 Å

37523

8wgz

EMDB-37523, PDB-8wgz:
MPOX E5 double hexamer ssDNA bound conformation
Method: EM (single particle) / Resolution: 3.22 Å

37524

8wh0

EMDB-37524, PDB-8wh0:
MPOX E5 hexamer ssDNA and AMP-PNP bound conformation
Method: EM (single particle) / Resolution: 2.51 Å

37526

8wh2

EMDB-37526, PDB-8wh2:
MPOX E5 hexamer 2ATP, 2ADP, and ssDNA binding comformation
Method: EM (single particle) / Resolution: 2.9 Å

37527

8wh3

EMDB-37527, PDB-8wh3:
MPOX E5 hexamer apo form
Method: EM (single particle) / Resolution: 2.87 Å

37528

8wh4

EMDB-37528, PDB-8wh4:
MPOX E5 hexamer ssDNA bound apo conformation
Method: EM (single particle) / Resolution: 3.03 Å

37530

8wh6

EMDB-37530, PDB-8wh6:
MPOX E5 hexamer ADP and ssDNA bound and clear primase domain conformation
Method: EM (single particle) / Resolution: 3.27 Å

Chemicals

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • monkeypox virus
  • spodoptera frugiperda (fall armyworm)
KeywordsDNA BINDING PROTEIN/DNA / Monkey pox / helicase / DNA replication / Complex / VIRAL PROTEIN / DNA BINDING PROTEIN-DNA complex / DNA BINDING PROTEIN

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