Structural insight into the signal transduction mechanism of TRAF6related proteins

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Tumor necrosis factor (TNF) is a well-known inflammatory cytokine that is implicatedin several autoimmune diseases such as rheumatoid arthritis. Here we show the firstcrystal structure of the TNF-TNFR2 complex. Structural differences between TNFR1 andTNFR2 are analyzed and discussed. This data will be key to the future development oflow-toxic TNFR1 selective therapies. In addition, we also reveal the formation of a TNFR2supra-complex on the cell surface. Aggregation of these receptors may contribute to thecurrently unidentified mechanism of TNFR superfamily signal initiation.Tumor necrosis factor receptor-associated factor 6 (TRAF6) transduces signals frommembers of the Toll/interleukin-1 (IL-1) receptor and TNFR families. Here we show thatthe first crystal structure of the TRAF6 binding protein. The TRAF6 binding protein formsa dimer.