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Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores
Open accessPublished version of a preprint
Abstract
Poxviruses are among the largest double-stranded DNA viruses, with members such as variola virus, monkeypox virus and the vaccination strain vaccinia virus (VACV). Knowledge about the structural proteins that form the viral core has remained sparse. While major core proteins have been annotated via indirect experimental evidence, their structures have remained elusive and they could not be assigned to individual core features. Hence, which proteins constitute which layers of the core, such as the palisade layer and the inner core wall, has remained enigmatic. Here we show, using a multi-modal cryo-electron microscopy (cryo-EM) approach in combination with AlphaFold molecular modeling, that trimers formed by the cleavage product of VACV protein A10 are the key component of the palisade layer. This allows us to place previously obtained descriptions of protein interactions within the core wall into perspective and to provide a detailed model of poxvirus core architecture. Importantly, we show that interactions within A10 trimers are likely generalizable over members of orthopox- and parapoxviruses.
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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
Fast and accurate protein structure search with Foldseek
van Kempen, M., Kim, S. S., Tumescheit, C., Mirdita, M., Lee, J., Gilchrist, C. L. M., Söding, J., & Steinegger, M. (2022) · doi:10.1101/2022.02.07.479398 · Cited by 2,598
Fast and accurate protein structure search with Foldseek
van Kempen, M., Kim, S. S., Tumescheit, C., Mirdita, M., Lee, J., Gilchrist, C. L. M., Söding, J., & Steinegger, M. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-01773-0 · Cited by 2,596
Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution
Schur, F. K. M., Hagen, W. J. H., Rumlová, M., Ruml, T., Müller, B., Kräusslich, H.-G., & Briggs, J. A. G. (2015) · Nature · doi:10.1038/nature13838 · Cited by 296
Self-citationRetrovirus maturation-an extraordinary structural transformation
Mattei, S., Schur, F. K., & Briggs, J. A. (2016) · Current Opinion in Virology · doi:10.1016/j.coviro.2016.02.008 · Cited by 72 · cited 1×
“This is reminiscent of the incomplete hexagonal lattice observed, for example, with Gag proteins in immature retroviruses (Mattei et al. 2016).”
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Metadata
- Authors
- Datler, J., Hansen, J. M., Thader, A., Schlögl, A., Bauer, L. W., Hodirnau, V.-V., & Schur, F. K. M.
- Affiliations
- Institute of Science and Technology Austria (AT)
- Corresponding author
- Schur, Florian K. M.
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2024-02-05
- Volume
- 31
- Issue
- 7
- Pages
- 1114-1123
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC11257981
- OpenAlex
- W4391540113
- Cited by
- 23
- References
- 5
- Citations by year
- 2026: 11 · 2025: 3 · 2024: 9
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Structural & Molecular Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Silicon Valley Community Foundation (10.13039/100014989)
- Institute of Science and Technology Austria
- Chan Zuckerberg Initiative
- Österreichischen Akademie der Wissenschaften
- Austrian Science Fund (P31445)
- Medizinische Universität Wien
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Poxvirus research and outbreaks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- poxvirus, vaccinia virus, viral core structure, palisade layer, core wall, orthopoxvirus, viral structural proteins
- MeSH terms
- Humans, Models, Molecular, Poxviridae, Vaccinia virus, Viral Core Proteins, Cryoelectron Microscopy, Protein Multimerization
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