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Structure paper

TitleStructural and functional insights into the helicase protein E5 of Mpox virus.
Journal, issue, pagesCell Discov, Vol. 10, Issue 1, Page 67, Year 2024
Publish dateJun 25, 2024
AuthorsWeizhen Zhang / Yusong Liu / Mengquan Yang / Jie Yang / Zhiwei Shao / Yanqing Gao / Xinran Jiang / Ruixue Cui / Yixi Zhang / Xin Zhao / Qiyuan Shao / Chulei Cao / Huili Li / Linxi Li / Hehua Liu / Haishan Gao / Jianhua Gan /
PubMed AbstractMpox virus (MPXV) can cause mpox in humans. Due to its quick and wide spread in the past two years, mpox has turned into a significant public health concern. Helicase E5 is a multi-domain protein; ...Mpox virus (MPXV) can cause mpox in humans. Due to its quick and wide spread in the past two years, mpox has turned into a significant public health concern. Helicase E5 is a multi-domain protein; its primer synthesis and DNA unwinding activity are required for genome uncoating and DNA replication of MPXV. However, the in vitro DNA unwinding activity has never been demonstrated. Here, we report the structural and biochemical studies of MPXV E5, showing that the full-length protein adopts an auto-inhibited conformation. Truncation of the N-terminus can recover the in vitro unwinding activity of E5 towards the forked DNA. Further structural analysis reveals that MPXV E5 shares a conserved mechanism in DNA unwinding and primer synthesis with the homologous proteins. These findings not only advance our understanding on the function of MPXV E5, but also provide a solid basis for the development of anti-poxvirus drugs.
External linksCell Discov / PubMed:38914567 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.39 - 3.32 Å
Structure data

EMDB-38394, PDB-8xj6:
The Cryo-EM structure of MPXV E5 apo conformation
Method: EM (single particle) / Resolution: 3.32 Å

EMDB-38395, PDB-8xj7:
The Cryo-EM structure of MPXV E5 in complex with DNA
Method: EM (single particle) / Resolution: 2.74 Å

EMDB-38396, PDB-8xj8:
The Cryo-EM structure of MPXV E5 C-terminal in complex with DNA
Method: EM (single particle) / Resolution: 2.67 Å

PDB-8xif:
The crystal structure of the AEP domain of VACV D5
Method: X-RAY DIFFRACTION / Resolution: 1.39 Å

PDB-8xig:
The crystal structure of the AEP domain of MPXV E5
Method: X-RAY DIFFRACTION / Resolution: 1.65 Å

Chemicals

ChemComp-PPV:
PYROPHOSPHATE

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

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

ChemComp-AN2:
AMP PHOSPHORAMIDATE

ChemComp-ZN:
Unknown entry

Source
  • monkeypox virus
  • vaccinia virus
KeywordsREPLICATION / primase / VACV / helicase

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