Crystal structure of marburg virus VP40 reveals a broad, basic patch for matrix assembly and a requirement of the n-terminal domain for immunosuppression

Shun Ichiro Oda, Takeshi Noda, Kaveesha J. Wijesinghe, Peter Halfmann, Zachary A. Bornholdt, Dafna M. Abelson, Tammy Armbrust, Robert V. Stahelin, Yoshihiro Kawaoka, Erica Ollmann Saphire

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Marburg virus (MARV), a member of the filovirus family, causes severe hemorrhagic fever with up to 90% lethality. MARV matrix protein VP40 is essential for assembly and release of newly copied viruses and also suppresses immune signaling in the infected cell. Here we report the crystal structure of MARV VP40. We found that MARV VP40 forms a dimer in solution, mediated by N-terminal domains, and that formation of this dimer is essential for budding of virus-like particles. We also found the N-terminal domain to be necessary and sufficient for immune antagonism. The C-terminal domains of MARV VP40 are dispensable for immunosuppression but are required for virus assembly. The C-terminal domains are only 16% identical to those of Ebola virus, differ in structure from those of Ebola virus, and form a distinct broad and flat cationic surface that likely interacts with the cell membrane during virus assembly.

Original languageEnglish (US)
Pages (from-to)1839-1848
Number of pages10
JournalJournal of virology
Volume90
Issue number4
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Oda, S. I., Noda, T., Wijesinghe, K. J., Halfmann, P., Bornholdt, Z. A., Abelson, D. M., Armbrust, T., Stahelin, R. V., Kawaoka, Y., & Saphire, E. O. (2016). Crystal structure of marburg virus VP40 reveals a broad, basic patch for matrix assembly and a requirement of the n-terminal domain for immunosuppression. Journal of virology, 90(4), 1839-1848. https://doi.org/10.1128/JVI.01597-15