4m0q | pdb_00004m0q
Ebola virus VP24 structure
Structural highlights
FunctionVP24_EBOZM Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways. Blocks the IFN-induced nuclear accumulation of host phosphorylated STAT1, by interacting with the STAT1-binding region of host importin alpha-1/KPNA1 protein, thereby inhibiting the latter. Without the activity of this protein, activated STAT1 would not enter the nucleus and be unable to activate IFN-induced genes. Plays a role in assembly of viral nucleocapsid and virion budding. May act as a minor matrix protein that plays a role in assembly of viral nucleocapsid and virion budding.[1] [2] [3] [4] Publication Abstract from PubMedKelch-like ECH-associated protein 1 (Keap1) is a ubiquitin E3 ligase specificity factor that targets transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) for ubiquitination and degradation. Disrupting Keap1-Nrf2 interaction stabilizes Nrf2, resulting in Nrf2 nuclear accumulation, binding to antioxidant response elements (AREs), and transcription of cytoprotective genes. Marburg virus (MARV) is a zoonotic pathogen that likely uses bats as reservoir hosts. We demonstrate that MARV protein VP24 (mVP24) binds the Kelch domain of either human or bat Keap1. This binding is of high affinity and 1:1 stoichiometry and activates Nrf2. Modeling based on the Zaire ebolavirus (EBOV) VP24 (eVP24) structure identified in mVP24 an acidic loop (K-loop) critical for Keap1 interaction. Transfer of the K-loop to eVP24, which otherwise does not bind Keap1, confers Keap1 binding and Nrf2 activation, and infection by MARV, but not EBOV, activates ARE gene expression. Therefore, MARV targets Keap1 to activate Nrf2-induced cytoprotective responses during infection. The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway.,Edwards MR, Johnson B, Mire CE, Xu W, Shabman RS, Speller LN, Leung DW, Geisbert TW, Amarasinghe GK, Basler CF Cell Rep. 2014 Mar 27;6(6):1017-25. doi: 10.1016/j.celrep.2014.01.043. Epub 2014 , Mar 13. PMID:24630991[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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