Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling.
Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub for RIG-I receptor proximal signal propagation. However, key components in the assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial localization and optimal activation are still largely undefined. Employing pooled RNAi and yeast two-hybrid screenings, we report that ... the mitochondrial adaptor protein tripartite motif (TRIM)14 provides a docking platform for the assembly of the mitochondrial signaling complex required for maximal activation of RIG-I-mediated signaling, consisting of WHIP and protein phosphatase PPP6C. Following viral infection, the ubiquitin-binding domain in WHIP bridges RIG-I with MAVS by binding to polyUb chains of RIG-I at lysine 164. The ATPase domain in WHIP contributes to stabilization of the RIG-I-dsRNA interaction. Moreover, phosphatase PPP6C is responsible for RIG-I dephosphorylation. Together, our findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG-I-mediated innate antiviral immunity.
Mesh Terms:
ATPases Associated with Diverse Cellular Activities, Animals, Carrier Proteins, Cell Line, Tumor, Cercopithecus aethiops, DEAD Box Protein 58, DNA-Binding Proteins, Humans, Immunity, Innate, Mitochondria, Mitochondrial Proteins, Multiprotein Complexes, Phosphoprotein Phosphatases, Signal Transduction, Vero Cells, Virus Diseases, Viruses
ATPases Associated with Diverse Cellular Activities, Animals, Carrier Proteins, Cell Line, Tumor, Cercopithecus aethiops, DEAD Box Protein 58, DNA-Binding Proteins, Humans, Immunity, Innate, Mitochondria, Mitochondrial Proteins, Multiprotein Complexes, Phosphoprotein Phosphatases, Signal Transduction, Vero Cells, Virus Diseases, Viruses
Mol. Cell
Date: Oct. 19, 2017
PubMed ID: 29053956
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