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 Stahelin, Yoshihiro Kawaoka, Erica Ollmann Saphire

Research output: Contribution to journalArticle

19 Citations (Scopus)

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

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Marburg virus
Marburgvirus
immunosuppression
crystal structure
Immunosuppression
Ebolavirus
Virus Assembly
Filoviridae
viral morphology
virus-like particles
Virion
fever
cell membranes
Fever
Cell Membrane
Viruses
viruses

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Crystal structure of marburg virus VP40 reveals a broad, basic patch for matrix assembly and a requirement of the n-terminal domain for immunosuppression. / Oda, Shun Ichiro; Noda, Takeshi; Wijesinghe, Kaveesha J.; Halfmann, Peter; Bornholdt, Zachary A.; Abelson, Dafna M.; Armbrust, Tammy; Stahelin, Robert; Kawaoka, Yoshihiro; Saphire, Erica Ollmann.

In: Journal of Virology, Vol. 90, No. 4, 2016, p. 1839-1848.

Research output: Contribution to journalArticle

Oda, SI, Noda, T, Wijesinghe, KJ, Halfmann, P, Bornholdt, ZA, Abelson, DM, Armbrust, T, Stahelin, R, Kawaoka, Y & Saphire, EO 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, vol. 90, no. 4, pp. 1839-1848. https://doi.org/10.1128/JVI.01597-15
Oda, Shun Ichiro ; Noda, Takeshi ; Wijesinghe, Kaveesha J. ; Halfmann, Peter ; Bornholdt, Zachary A. ; Abelson, Dafna M. ; Armbrust, Tammy ; Stahelin, Robert ; Kawaoka, Yoshihiro ; Saphire, Erica Ollmann. / Crystal structure of marburg virus VP40 reveals a broad, basic patch for matrix assembly and a requirement of the n-terminal domain for immunosuppression. In: Journal of Virology. 2016 ; Vol. 90, No. 4. pp. 1839-1848.
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