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Structural basis for the assembly of the DNA polymerase holoenzyme from a monkeypox virus variant
Open accessPublished version of a preprint
Abstract
The ongoing global pandemic caused by a variant of the monkeypox (or mpox) virus (MPXV) has prompted widespread concern. The MPXV DNA polymerase holoenzyme, consisting of F8, A22, and E4, is vital for replicating the viral genome and represents a crucial target for the development of antiviral drugs. However, the assembly and working mechanism for the DNA polymerase holoenzyme of MPXV remains elusive. Here, we present the cryo–electron microscopy (cryo-EM) structure of the DNA polymerase holoenzyme at an overall resolution of 3.5 Å. Unexpectedly, the holoenzyme is assembled as a dimer of heterotrimers, of which the extra interface between the thumb domain of F8 and A22 shows a clash between A22 and substrate DNA, suggesting an autoinhibition state. Addition of exogenous double-stranded DNA shifts the hexamer into trimer exposing DNA binding sites, potentially representing a more active state. Our findings provide crucial steps toward developing targeted antiviral therapies for MPXV and related viruses.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Flagged first, then by citations
Research works printed but not linked: 59
- 10.1038/s41577-022-00775-4 · DOI
- 10.1016/j.bsheal.2022.11.001 · DOI
- 10.1038/nrmicro1099 · DOI
- 10.1128/br.37.1.1-18.1973 · DOI
- 10.1001/jama.281.22.2127 · DOI
- 10.1099/vir.0.81215-0 · DOI
- 10.3390/v12111257 · DOI
- 10.1371/journal.pntd.0007791 · DOI
- 10.1038/s41591-022-01907-y · DOI
- 10.1001/jama.2022.10802 · DOI
- 10.1093/ije/17.3.643 · DOI
- 10.3390/pathogens11080924 · DOI
- P. Traktman, The enzymology of poxvirus DNA replication. Curr. Top. Microbiol. Immunol. 163, 93–123 (1990).
- 10.1101/cshperspect.a010199 · DOI
- 10.1146/annurev-virology-091919-104752 · DOI
- 10.1074/jbc.M511239200 · DOI
- 10.1038/s41467-017-01542-z · DOI
- 10.1073/pnas.2009415117 · DOI
- 10.1016/j.jmb.2021.167009 · DOI
- 10.1128/JVI.01533-12 · DOI
- 10.1128/JVI.01435-10 · DOI
- 10.1371/journal.ppat.1003978 · DOI
- 10.1074/jbc.M115.648352 · DOI
- 10.1016/S0166-3542(02)00196-1 · DOI
- 10.3390/v2122681 · DOI
- 10.1128/AAC.46.5.1329-1335.2002 · DOI
- 10.1128/AAC.49.8.3153-3162.2005 · DOI
- 10.1016/j.jaut.2022.102928 · DOI
- 10.1128/jvi.66.1.534-547.1992 · DOI
- 10.1128/jvi.1.3.550-558.1967 · DOI
- 10.1016/j.virusres.2017.01.027 · DOI
- 10.1126/science.aav7003 · DOI
- 10.1016/S0092-8674(00)81647-5 · DOI
- 10.1016/S1097-2765(00)80422-0 · DOI
- 10.1016/j.jmb.2009.09.066 · DOI
- 10.1074/jbc.M111.222216 · DOI
- 10.1091/mbc.e05-12-1179 · DOI
- 10.1128/JVI.00178-16 · DOI
- 10.1016/S0021-9258(18)47408-X · DOI
- 10.1016/0092-8674(81)90422-0 · DOI
- 10.1073/pnas.0709276104 · DOI
- 10.1007/BF02451789 · DOI
- 10.1126/science.ade6360 · DOI
- 10.1016/S0166-3542(02)00008-6 · DOI
- 10.1128/AAC.05983-11 · DOI
- 10.1038/sj.jid.5701161 · DOI
- 10.2165/00003495-199652020-00006 · DOI
- 10.1038/nsmb.1663 · DOI
- 10.1093/nar/gkg520 · DOI
- 10.1016/0006-2952(72)90319-X · DOI
- 10.1038/nmeth.4193 · DOI
- 10.7554/eLife.06980 · DOI
- 10.1016/j.jsb.2015.11.003 · DOI
- 10.1016/j.jsb.2012.09.006 · DOI · Paper page
- 10.1038/nmeth.4169 · DOI · Paper page
- 10.1016/j.jmb.2003.07.013 · DOI · Paper page
- 10.1016/j.ultramic.2013.06.004 · DOI
- 10.1107/S0907444910007493 · DOI · Paper page
- 10.1107/S0907444909052925 · DOI · Paper page
Cited by
Sorted by citations
Structure and flexibility of the DNA polymerase holoenzyme of vaccinia virus
Burmeister, W. P., Boutin, L., Balestra, A. C., Gröger, H., Ballandras-Colas, A., Hutin, S., Kraft, C., Grimm, C., Böttcher, B., Fischer, U., et al. (2024) · PLOS Pathogens · doi:10.1371/journal.ppat.1011652 · Cited by 3
Metadata
- Authors
- Li, Y., Shen, Y., Hu, Z., & Yan, R.
- Affiliations
- Westlake University (CN)
- Southern University of Science and Technology (CN)
- Corresponding author
- Yan, Renhong
- Venue
- Science Advances
- Published
- 2023-04-21
- Volume
- 9
- Issue
- 16
- Pages
- eadg2331-eadg2331
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC10115419
- OpenAlex
- W4366382766
- Cited by
- 31
- References
- 1
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 11 · 2023: 3
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Science Advances (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Science, Technology and Innovation Commission of Shenzhen Municipality
- Southern University of Science and Technology
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Poxvirus research and outbreaks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- monkeypox virus, autoinhibition, thumb domain, DNA binding, viral genome replication, antiviral drug targets, cryo-EM structure
- MeSH terms
- DNA-Directed DNA Polymerase, Humans, Monkeypox virus, Cryoelectron Microscopy, Mpox (monkeypox), Mpox, Monkeypox
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