The Ebola Virus Nucleoprotein Recruits the Host PP2A-B56 Phosphatase to Activate Transcriptional Support Activity of VP30
Open accessAbstract
Transcription of the Ebola virus genome depends on the viral transcription factor VP30 in its unphosphorylated form, but the underlying molecular mechanism of VP30 dephosphorylation is unknown. Here we show that the Ebola virus nucleoprotein (NP) recruits the host PP2A-B56 protein phosphatase through a B56-binding LxxIxE motif and that this motif is essential for VP30 dephosphorylation and viral transcription. The LxxIxE motif and the binding site of VP30 in NP are in close proximity, and both binding sites are required for the dephosphorylation of VP30. We generate a specific inhibitor of PP2A-B56 and show that it suppresses Ebola virus transcription and infection. This work dissects the molecular mechanism of VP30 dephosphorylation by PP2A-B56, and it pinpoints this phosphatase as a potential target for therapeutic intervention.
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An additional 15% of proteins identified in the screen are interactors of proteins with validated or predicted LxxIxE docking motifs.
“an additional 15% of proteins identified in our screen are interactors of proteins with validated or predicted LxxIxE docking motifs46,48 (Fig. 6D and Supplementary Data 4).”
From Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A (2023) · cites this paper as [46]
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- Authors
- Kruse, T., Biedenkopf, N., Hertz, E. P. T., Dietzel, E., Stalmann, G., López-Méndez, B., Davey, N. E., Nilsson, J., & Becker, S.
- Affiliations
- University of Copenhagen (DK)
- Philipps University of Marburg (DE)
- University College Dublin (IE)
- Corresponding author
- Nilsson, Jakob
- Becker, Stephan
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 69
- Issue
- 1
- Pages
- 136-145.e6
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2781091353
- Cited by
- 92
- References
- 24
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 16 · 2020: 13 · 2019: 12 · 2018: 7
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Novo Nordisk Foundation (NNF14CC0001)
- Danish Cancer Society (R72-A4351-13-S2, R124-A7827-15-S2)
- Deutsche Forschungsgemeinschaft (DFG)
- Collaborative Research Center (CRC) (1021, subproject A02)
- German Center of Infection Research (DZIF)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Keywords
- Ebola virus, nucleocapsid protein, VP30, viral transcription, host-virus interaction, phosphatase inhibitors, antiviral drug targets
- MeSH terms
- Animals, Chlorocebus aethiops, HeLa Cells, Humans, Nucleoproteins, Phosphorylation, RNA, Viral, Transcription Factors, Transcription, Genetic, Vero Cells, Viral Proteins, Virus Replication, Ebolavirus, Cell Line, Tumor, Protein Phosphatase 2, Protein Interaction Domains and Motifs, HEK293 Cells
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