8HWE

Cryo-EM Structure of D5 ATP-ADP form

Summary for 8HWE

• Entry DOI: 10.2210/pdb8hwe/pdb
• EMDB information: 35055
• Descriptor: Primase D5, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: mpvx, viral protein
• Biological source: Monkeypox virus
• Total number of polymer chains: 6
• Total formula weight: 545942.70

Authors

Li, Y.N.,Zhu, J.,Guo, Y.Y.,Yan, R.H. (deposition date: 2022-12-29, release date: 2024-01-10, Last modification date: 2024-01-31)

Primary citation

Li, Y.,Zhu, J.,Guo, Y.,Yan, R.
Structural insight into the assembly and working mechanism of helicase-primase D5 from Mpox virus.
Nat.Struct.Mol.Biol., 31:68-81, 2024

PubMed Abstract: The Mpox pandemic, caused by the Mpox virus (or monkeypox virus, MPXV), has gained global attention. The D5 protein, a putative helicase-primase found in MPXV, plays a vital role in viral replication and genome uncoating. Here we determined multiple cryo-EM structures of full-length hexameric D5 in diverse states. These states were captured during ATP hydrolysis while moving along the single-stranded DNA (ssDNA) track. Through comprehensive structural analysis combined with the helicase activity system, we revealed that when the primase domain is truncated or the interaction between the primase and helicase domains is disrupted, the double-stranded DNA (dsDNA) unwinds into ssDNA, suggesting a critical regulatory role of the primase domain. Two transition states bound with ssDNA substrate during unwinding reveals that two ATP molecules were consumed to drive DNA moving forward two nucleotides. Collectively, our findings shed light on the molecular mechanism that links ATP hydrolysis to the DNA unwinding in poxviruses.

PubMed: 38177671
DOI: 10.1038/s41594-023-01142-0

Experimental method

ELECTRON MICROSCOPY (3.3 Å)