Dynamic Regulation of MAVS Protein Function via Reversible Oxidation at Cys79in Response to Oxidant Stimuli

Abstract

AbstractDeciphering the intricacies of redox-mediated protein dynamics hinges on the pivotal role of reversible cysteine residue oxidation. At the nexus of the orchestration of type I interferon responses, the mitochondrial antiviral signaling protein (MAVS) assumes a central position, in coordinating the defense against both pathogens and endogenous danger molecules. Despite compelling evidence linking reactive oxygen species to MAVS pathways, the underlying mechanisms remain elusive. Here, we unveiled oxidative stress-induced reversible oxidation of cysteine within MAVS and identify sulfenylation as a prominent modification. We pinpoint Cys79as a target susceptible to oxidation under specific oxidant conditions. Intriguingly, in conditions of oxidative stress sufficient to initiate MAVS-dependentIFNBpromoter transactivation, Cys79modification plays an inhibitory role, unraveling a nuanced interplay between redox regulation and MAVS activation. Our comprehensive insights propose novel, redox-driven mechanisms underlying the intricate dynamics of MAVS, a pivotal adaptor in cellular defense.