TY - JOUR
T1 - TRAF3 signaling
T2 - Competitive binding and evolvability of adaptive viral molecular mimicry
AU - Guven-Maiorov, Emine
AU - Keskin, Ozlem
AU - Gursoy, Attila
AU - VanWaes, Carter
AU - Chen, Zhong
AU - Tsai, Chung Jung
AU - Nussinov, Ruth
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - Antiviral immunity
KW - Cancer
KW - Evolvable
KW - Host-pathogen interactions
KW - Inflammation
KW - Structure
UR - http://www.scopus.com/inward/record.url?scp=84973878591&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2016.05.021
DO - 10.1016/j.bbagen.2016.05.021
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C2 - 27208423
AN - SCOPUS:84973878591
SN - 0304-4165
VL - 1860
SP - 2646
EP - 2655
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 11
ER -