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Crystal Structure of Marburg virus VP40 DimerCrystal Structure of Marburg virus VP40 Dimer
Structural highlights
Function[VP40_MABVM] Promotes virus assembly and budding by interacting with host proteins of the multivesicular body pathway. May facilitate virus budding by interacting with the nucleocapsid and the plasma membrane. Specific interactions with membrane-associated GP and VP24 during the budding process may also occur. May play a role in genome replication (By similarity). Publication Abstract from PubMedMarburg virus (MARV), a member of the filovirus family, causes severe hemorrhagic fever with up to 90% lethality. The 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 find 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 find 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. IMPORTANCE: Marburg virus, a cousin of Ebola virus, causes severe hemorrhagic fever with up to 90% lethality in recent outbreaks. Molecular structures and visual images of the proteins of Marburg virus are essential to development of antiviral drugs. One key protein in the Marburg virus life cycle is VP40, which both assembles the virus and suppresses the immune system. Here we provide the molecular structure of Marburg virus VP40, illustrate differences with VP40 of Ebola virus, and reveal surfaces by which Marburg VP40 assembles progeny and suppresses immune function. Crystal structure of Marburg virus VP40: matrix assembly and immunosuppression.,Oda SI, Noda T, Wijesinghe KJ, Halfmann P, Bornholdt ZA, Abelson DM, Armbrust T, Stahelin RV, Kawaoka Y, Saphire EO J Virol. 2015 Dec 9. pii: JVI.01597-15. PMID:26656687[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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