2. Academic Validation
  3. Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated Antiviral Signaling

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

  • Mol Cell. 2017 Oct 19;68(2):293-307.e5. doi: 10.1016/j.molcel.2017.09.035.
Peng Tan 1,  Lian He 2,  Jun Cui 3,  Chen Qian 4,  Xin Cao 4,  Meng Lin 4,  Qingyuan Zhu 4,  Yinyin Li 1,  Changsheng Xing 4,  Xiao Yu 4,  Helen Y Wang 5,  Rong-Fu Wang 6
Affiliations

Affiliations

  • 1 Institute 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.
  • 2 Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA.
  • 3 Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, College of Life Sciences, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou 510275, China.
  • 4 Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA.
  • 5 Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: [email protected].
  • 6 Institute 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; Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY 10065, USA. Electronic address: [email protected].
PMID: 29053956 DOI: 10.1016/j.molcel.2017.09.035
Abstract

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.

Keywords

ATPase domain; K63 ubiquitination; RIG-I-like receptor signaling; dephosphorylation; mitochondrial signalosome; ubiquitin binding.

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