14-3-3 scaffold proteins mediate the inactivation of trim25 and inhibition of the type I interferon response by herpesvirus deconjugases

• DOI: 10.1371/journal.ppat.1008146
• Publication Date: 2019-11-11T13:34:34Z
• Authors: Soham Gupta; Päivi Ylä-Anttila; Tatyana Sandalova; Renhua Sun; Adnane Achour; Maria G. Masucci
• Keywords: Deubiquitinating enzyme

The 14-3-3 molecular scaffolds promote type I interferon (IFN) responses by stabilizing the interaction of RIG-I with TRIM25 ligase. Viruses have evolved unique strategies to halt this cellular response support their replication and spread. Here, we report that ubiquitin deconjugase (DUB) encoded in N-terminus Epstein-Barr virus (EBV) large tegument protein BPLF1 harnesses molecules autoubiquitination sequestration ligase into inactive aggregates. Catalytically induced K48-linked degradation while was mono- or di-ubiquitinated presence active viral enzyme formed cytosolic aggregates decorated autophagy receptor p62/SQSTM1. Aggregate formation inhibition IFN were abolished mutations solvent exposed residues helix-2 prevented binding preserving both catalytic activity TRIM25. interacted Coiled-Coil (CC) domain vitro pulldown, CC B-box domains, suggesting positions at ends dimer, close known sites. Our findings provide a understanding mechanism which deubiquitinase inhibits emphasize role proteins modulating antiviral defenses.