Essential and multifunctional mpox virus E5 helicase-primase in double and single hexamer
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<sup>249</sup>, Lys<sup>286</sup>, Lys<sup>315</sup>, and Lys<sup>317</sup>. 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.
Authors
- Changjiang Dong (ORCID: https://orcid.org/0000-0002-7020-5648)
- Biao Yang (ORCID: https://orcid.org/0000-0002-6002-3330)
- Yuanyuan Zhang (ORCID: https://orcid.org/0000-0001-6972-5606)
- Danyang Li (ORCID: https://orcid.org/0000-0003-2543-3008)
- Zhengyu Zhang (ORCID: https://orcid.org/0000-0001-5035-1229)
- Yunxia Xu
- Yaqi Wu (ORCID: https://orcid.org/0000-0003-4380-3009)
- Xiaoying Wu (ORCID: https://orcid.org/0000-0002-5486-9938)
- Yaxue Yang
- Kaiting Gao
Institutions
- Wuhan University (CN)
- Zhongnan Hospital of Wuhan University (CN)
Publication Details
- Journal
- Science Advances
- Published
- 2024-08-21
- DOI
- https://doi.org/10.1126/sciadv.adl1150
- Citations
- 3
- Primary Topic
- Poxvirus research and outbreaks
- Type
- article
- Field-Weighted Citation Impact
- 0.88
Funders
- National Natural Science Foundation of China
- Wuhan University