Department of Chemical and Biological EngineeringDepartment of Computer Engineering2024-11-1020160304-416510.1016/j.bbagen.2016.05.0212-s2.0-84973878591http://dx.doi.org/10.1016/j.bbagen.2016.05.021https://hdl.handle.net/20.500.14288/16159Background: 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-kappa B 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.BiochemistryMolecular BiologyBiophysicsJournal Article1872-8006383825000005Q24570