SNAP output for PDB entry 8wgy [SNAP web server]

PDB-id

8wgy; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein-DNA

Method

cryo-EM (2.91 Å)

Summary

Mpox e5 hexamer amp-pnp and ssDNA bound form with clear primase domain

Reference

Xu Y, Wu Y, Zhang Y, Gao K, Wu X, Yang Y, Li D, Yang B, Zhang Z, Dong C (2024): "Essential and multifunctional mpox virus E5 helicase-primase in double and single hexamer." Sci Adv, 10, eadl1150. doi: 10.1126/sciadv.adl1150.

Abstract

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 Arg₂₄₉, Lys₂₈₆, Lys₃₁₅, and Lys₃₁₇. 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.