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Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling

Peng Tan1, Lian He2, Jun Cui3

  • 1Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA; Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.

Molecular Cell
|October 21, 2017
PubMed

Insights

Researchers identified a new protein complex, WHIP-TRIM14-PPP6C, crucial for innate antiviral immunity. This complex assembles on mitochondria, enhancing RIG-I receptor activation against viral infections.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Mitochondrial antiviral signaling platform protein (MAVS) is central to RIG-I receptor signaling.
  • Key components regulating MAVS mitochondrial platform assembly and RIG-I activation remain largely unknown.

Purpose of the Study:

  • To identify novel components involved in the assembly of the MAVS mitochondrial signaling complex.
  • To elucidate the mechanism by which these components regulate RIG-I-mediated antiviral immunity.

Main Methods:

  • Pooled RNA interference (RNAi) screening.
  • Yeast two-hybrid screening.
  • Biochemical assays to study protein interactions and modifications.

Main Results:

  • Tripartite motif (TRIM)14 acts as a docking platform for WHIP and protein phosphatase PPP6C, forming a mitochondrial signalosome.
  • WHIP bridges RIG-I to MAVS via its ubiquitin-binding domain, interacting with RIG-I polyubiquitin chains.
  • WHIP's ATPase domain stabilizes RIG-I-dsRNA interaction, while PPP6C dephosphorylates RIG-I.

Conclusions:

  • The WHIP-TRIM14-PPP6C complex is essential for maximal RIG-I activation and innate antiviral immunity.
  • This study defines a novel mitochondrial signalosome critical for antiviral defense pathways.
Keywords:
ATPase domainK63 ubiquitinationRIG-I-like receptor signalingdephosphorylationmitochondrial signalosomeubiquitin binding

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