4M0Q

Ebola virus VP24 structure

Summary for 4M0Q

• Entry DOI: 10.2210/pdb4m0q/pdb
• Descriptor: Membrane-associated protein VP24 (2 entities in total)
• Functional Keywords: ebola virus virulence factor, viral protein
• Biological source: Zaire ebolavirus (ZEBOV)
• Cellular location: Virion membrane ; Peripheral membrane protein : Q05322
• Total number of polymer chains: 2
• Total formula weight: 51842.14

Authors

Xu, W.,Leung, D.W.,Borek, D.,Amarasinghe, G.K. (deposition date: 2013-08-01, release date: 2014-03-19, Last modification date: 2023-09-20)

Primary citation

Edwards, M.R.,Johnson, B.,Mire, C.E.,Xu, W.,Shabman, R.S.,Speller, L.N.,Leung, D.W.,Geisbert, T.W.,Amarasinghe, G.K.,Basler, C.F.
The Marburg Virus VP24 Protein Interacts with Keap1 to Activate the Cytoprotective Antioxidant Response Pathway.
Cell Rep, 6:1017-1025, 2014

PubMed Abstract: Kelch-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.

PubMed: 24630991
DOI: 10.1016/j.celrep.2014.01.043

Experimental method

X-RAY DIFFRACTION (1.921 Å)