title: TRAF3 signaling: Competitive binding and evolvability of adaptive viral molecular mimicry.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702,USA. Electronic address: emine.guven-maiorov@nih.gov.
authors.forename: Emine
authors.initials: E
authors.lastname: Guven-Maiorov
authors.affiliation: Department of Chemical and Biological Engineering, Koc University, Istanbul, Turkey; Center for Computational Biology and Bioinformatics, Koc University, Istanbul, Turkey. Electronic address: okeskin@ku.edu.tr.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Keskin
authors.affiliation: Center for Computational Biology and Bioinformatics, Koc University, Istanbul, Turkey; Department of Computer Engineering, Koc University, Istanbul, Turkey. Electronic address: agursoy@ku.edu.tr.
authors.forename: Attila
authors.initials: A
authors.lastname: Gursoy
authors.affiliation: Clinical Genomic Unit, Head and Neck Surgery Branch, National Institute on Deafness and Communication Disorders, NIH, Bethesda, MD 20892, USA. Electronic address: vanwaesc@nidcd.nih.gov.
authors.forename: Carter
authors.initials: C
authors.lastname: VanWaes
authors.affiliation: Clinical Genomic Unit, Head and Neck Surgery Branch, National Institute on Deafness and Communication Disorders, NIH, Bethesda, MD 20892, USA. Electronic address: chenz@nidcd.nih.gov.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702,USA. Electronic address: tsaic@mail.nih.gov.
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Tsai
authors.affiliation: Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD 21702,USA; Sackler Inst. of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: nussinor@helix.nih.gov.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
mesh_terms: D001667:Binding, Competitive / Q000502:physiology*; D006801:Humans; D018716:Molecular Mimicry / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D014777:Virus Diseases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D048008:TNF Receptor-Associated Factor 3; C090656:TRAF3 protein, human; D014764:Viral Proteins
keywords: Antiviral immunity; Cancer; Evolvable; Host-pathogen interactions; Inflammation; Structure