Role of K-Loop Cysteine Residues in the Marburg Virus Protein VP24-Human Keap1 Complex

Abstract

Binding of the Marburg virus protein VP24 to the human Keap1 protein allows the nuclear accumulation of Nrf2, activating cytoprotective antioxidant response pathways during the viral life cycle. We investigate the molecular level details of VP24-Keap1 interactions for both Marburg and Ebola VP24. Our results show that the presence of the cysteine residues in the K-loop region of mVP24 provides strong interfacial interactions with Keap1, including hydrogen bonding and S-H··· interactions, facilitating the formation of a stable complex with Marburg VP24. These cysteine residues are not present in eVP24, which does not form a stable complex with Keap1. These results provide insights into how the Marburg virus, but not Ebola, is able to activate the antioxidant response pathways through direct interactions with Keap1.