Fig. 6.

Structural details of TRAF3 interactions revealed how TRAF3 inhibits both the canonical and non-canonical NF-κB pathways. Structural details of TRAF3 interactions corrected critical misinterpretation and unravel what may happen in actual scenario. In TLR signaling, it was assumed that TRAF3 inhibits directly TRAF6, but structural data show that it inhibits the MyD88-TRAF6 interaction and hence prevents activation of the canonical NF-κB pathway. In TNFR signaling, the presumption was that TRAF3 blocks NIK; however structural data suggest that TRAF3-TNFR interaction prevents TRAF3-NIK association. Black lines show what was assumed before and red lines show what is revealed by the structural details of our models.