8XJ6

The Cryo-EM structure of MPXV E5 apo conformation

Summary for 8XJ6

• Entry DOI: 10.2210/pdb8xj6/pdb
• EMDB information: 38394
• Descriptor: Monkeypox virus E5, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, AMP PHOSPHORAMIDATE, ... (4 entities in total)
• Functional Keywords: primase, helicase, replication
• Biological source: Monkeypox virus
• Total number of polymer chains: 6
• Total formula weight: 545786.12

Authors

Zhang, W.,Liu, Y.,Gao, H.,Gan, J. (deposition date: 2023-12-20, release date: 2024-05-01, Last modification date: 2024-07-03)

Primary citation

Zhang, W.,Liu, Y.,Yang, M.,Yang, J.,Shao, Z.,Gao, Y.,Jiang, X.,Cui, R.,Zhang, Y.,Zhao, X.,Shao, Q.,Cao, C.,Li, H.,Li, L.,Liu, H.,Gao, H.,Gan, J.
Structural and functional insights into the helicase protein E5 of Mpox virus.
Cell Discov, 10:67-67, 2024

PubMed Abstract: 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.

PubMed: 38914567
DOI: 10.1038/s41421-024-00680-1

Experimental method

ELECTRON MICROSCOPY (3.32 Å)