ArticleJournal of molecular biology2016
Dimerization Controls Marburg Virus VP24-dependent Modulation of Host Antioxidative Stress Responses.
Article in Journal of molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
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- Design of a novel multi-epitope vaccine against Marburg virus using immunoinformatics studies.BMC biotechnology · 2024Article
- The Role of Ebola Virus VP24 Nuclear Trafficking Signals in Infectious Particle Production.bioRxiv : the preprint server for biology · 2024Article
- Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription.Cell reports · 2021Article
- Mass Spectrometry-Based Structural Virology.Analytical chemistry · 2021Review
- Annexin A2 depletion exacerbates the intracerebral microhemorrhage induced by acute rickettsia and Ebola virus infections.PLoS neglected tropical diseases · 2020Article
- Impact of Měnglà Virus Proteins on Human and Bat Innate Immune Pathways.Journal of virology · 2020Article
- Small Molecule Compounds That Inhibit Antioxidant Response Gene Expression in an Inducer-Dependent Manner.ACS infectious diseases · 2020Article
- Development of a Cell-Permeable Cyclic Peptidyl Inhibitor against the Keap1-Nrf2 Interaction.The Journal of organic chemistry · 2020Article
- Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors-The Current Status.Frontiers in immunology · 2020Review
- Interlaboratory Comparison of Hydrogen-Deuterium Exchange Mass Spectrometry Measurements of the Fab Fragment of NISTmAb.Analytical chemistry · 2019Article
- Current status of small molecule drug development for Ebola virus and other filoviruses.Current opinion in virology · 2019Review
- Virus and host interactions critical for filoviral RNA synthesis as therapeutic targets.Antiviral research · 2019Review
- Recent advances in marburgvirus research.F1000Research · 2019Review
- The entropic force generated by intrinsically disordered segments tunes protein function.Nature · 2018Article
- MRI Is a DNA Damage Response Adaptor during Classical Non-homologous End Joining.Molecular cell · 2018Article
- Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway.Nature immunology · 2018Article
- Therapeutic Modulation of Virus-Induced Oxidative Stress via the Nrf2-Dependent Antioxidative Pathway.Oxidative medicine and cellular longevity · 2018Review
- A Sensitive in Vitro High-Throughput Screen To Identify Pan-filoviral Replication Inhibitors Targeting the VP35-NP Interface.ACS infectious diseases · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola virus (EBOV), causes lethal hemorrhagic fever with case fatality rates that have exceeded 50% in some outbreaks. Within an infected cell, there are numerous host-viral interactions that contribute to the outcome of infection. Recent studies identified MARV protein 24 (mVP24) as a modulator of the host antioxidative responses, but the molecular mechanism remains unclear. Using a combination of biochemical and mass spectrometry studies, we show that mVP24 is a dimer in solution that directly binds to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) to regulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2). This interaction between Keap1 and mVP24 occurs through the Kelch interaction loop (K-Loop) of mVP24 leading to upregulation of antioxidant response element transcription, which is distinct from other Kelch binders that regulate Nrf2 activity. N-terminal truncations disrupt mVP24 dimerization, allowing monomeric mVP24 to bind Kelch with higher affinity and stimulate higher antioxidative stress response element (ARE) reporter activity. Mass spectrometry-based mapping of the interface revealed overlapping binding sites on Kelch for mVP24 and the Nrf2 proteins. Substitution of conserved cysteines, C209 and C210, to alanine in the mVP24 K-Loop abrogates Kelch binding and ARE activation. Our studies identify a shift in the monomer-dimer equilibrium of MARV VP24, driven by its interaction with Keap1 Kelch domain, as a critical determinant that modulates host responses to pathogenic Marburg viral infections.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.