Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores

Datler J, Hansen J, Thader A, Schlögl A, Bauer LW, Hodirnau V-V, Schur FK. 2024. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. Nature Structural & Molecular Biology.


Journal Article | Epub ahead of print | English
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.
Publishing Year
Date Published
2024-02-05
Journal Title
Nature Structural & Molecular Biology
Acknowledgement
We thank A. Bergthaler (Research Center for Molecular Medicine of the Austrian Academy of Sciences) for providing VACV WR. We thank A. Nicholas and his team at the ISTA proteomics facility, and S. Elefante at the ISTA Scientific Computing facility for their support. We also thank F. Fäßler, D. Porley, T. Muthspiel and other members of the Schur group for support and helpful discussions. We also thank D. Castaño-Díez for support with Dynamo. We thank D. Farrell for his help optimizing the Rosetta protocol to refine the atomic model into the cryo-EM map with symmetry. F.K.M.S. acknowledges support from ISTA and EMBO. F.K.M.S. also received support from the Austrian Science Fund (FWF) grant P31445. This publication has been made possible in part by CZI grant DAF2021-234754 and grant https://doi.org/10.37921/812628ebpcwg from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (funder https://doi.org/10.13039/100014989) awarded to F.K.M.S. This research was also supported by the Scientific Service Units (SSUs) of ISTA through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), and the Electron Microscopy Facility (EMF). We also acknowledge the use of COSMIC45 and Colabfold46.
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Cite this

Datler J, Hansen J, Thader A, et al. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. Nature Structural & Molecular Biology. 2024. doi:10.1038/s41594-023-01201-6
Datler, J., Hansen, J., Thader, A., Schlögl, A., Bauer, L. W., Hodirnau, V.-V., & Schur, F. K. (2024). Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. Nature Structural & Molecular Biology. Springer Nature. https://doi.org/10.1038/s41594-023-01201-6
Datler, Julia, Jesse Hansen, Andreas Thader, Alois Schlögl, Lukas W Bauer, Victor-Valentin Hodirnau, and Florian KM Schur. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” Nature Structural & Molecular Biology. Springer Nature, 2024. https://doi.org/10.1038/s41594-023-01201-6.
J. Datler et al., “Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores,” Nature Structural & Molecular Biology. Springer Nature, 2024.
Datler J, Hansen J, Thader A, Schlögl A, Bauer LW, Hodirnau V-V, Schur FK. 2024. Multi-modal cryo-EM reveals trimers of protein A10 to form the palisade layer in poxvirus cores. Nature Structural & Molecular Biology.
Datler, Julia, et al. “Multi-Modal Cryo-EM Reveals Trimers of Protein A10 to Form the Palisade Layer in Poxvirus Cores.” Nature Structural & Molecular Biology, Springer Nature, 2024, doi:10.1038/s41594-023-01201-6.
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