TRAF3 signaling: Competitive binding and evolvability of adaptive viral molecular mimicry

• Published in: Biochimica et biophysica acta Vol. 1860; no. 11; pp. 2646 - 2655
• Main Authors: Guven-Maiorov, Emine, Keskin, Ozlem, Gursoy, Attila, VanWaes, Carter, Chen, Zhong, Tsai, Chung-Jung, Nussinov, Ruth
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2016
• Subjects: Antiviral immunity; antiviral properties; antiviral proteins; Binding, Competitive - physiology; Cancer; Evolvable; Host-pathogen interactions; Humans; Inflammation; molecular mimicry; Molecular Mimicry - physiology; NF-kappa B - metabolism; pathogens; Protein Binding - physiology; signal transduction; Signal Transduction - physiology; Structure; TNF Receptor-Associated Factor 3 - metabolism; transcription factor NF-kappa B; tumor necrosis factors; viral proteins; Viral Proteins - metabolism; Virus Diseases - metabolism; Inflammation; Evolvable; Structure; Cancer; Antiviral immunity; Host-pathogen interactions
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2016.05.021

Background: The tumor necrosis factor receptor (TNFR) associated factor 3 (TRAF3) is a key node in innate and adaptive immune signaling pathways. TRAF3 negatively regulates the activation of the canonical and non-canonical NF-κB pathways and is one of the key proteins in antiviral immunity. Scope of Review: Here we provide a structural overview of TRAF3 signaling in terms of its competitive binding and consequences to the cellular network. For completion, we also include molecular mimicry of TRAF3 physiological partners by some viral proteins. Major Conclusions: By out-competing host partners, viral proteins aim to subvert TRAF3 antiviral action. Mechanistically, dynamic, competitive binding by the organism's own proteins and same-site adaptive pathogen mimicry follow the same conformational selection principles. General Significance: Our premise is that irrespective of the eliciting event – physiological or acquired pathogenic trait – pathway activation (or suppression) may embrace similar conformational principles. However, even though here we largely focus on competitive binding at a shared site, similar to physiological signaling other pathogen subversion mechanisms can also be at play. This article is part of a Special Issue entitled “System Genetics” Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. •TRAF3 has a key role in antiviral immune response.•TRAF3 binds to several partners through the same or overlapping interfaces.•Viruses subvert host immunity by mimicking the binding surfaces of its proteins.•Viral proteins also target the same binding site on TRAF3.•Binding of viral proteins to TRAF3 competitively displaces its host partners.