LIG_TRAF6

TNFR-associated factors (TRAFs) constitute a family of six adaptor proteins that associated with TNF family receptors. Several TRAF proteins interact directly with the intracellular regions of various TNF cytokine receptors, including CD27, CD30, CD40, TNFR2, lymphotoxin beta-receptor, and the Herpes virus entry mediator. The unique biological function of TRAF6 is mainly determinate by its TRAF domain, which does not interact with the peptide motifs that are recognized by the other TRAFs. TRAF6 interacts with the cytoplasmic domain of RANK, CD40 and with interleukin-1 receptor-associated kinase 1 and 2. It was demonstrated that RANK interacts with TRAF6 via a novel interaction motif (Darnay,1999). Ye,2002 solved the crystal structure of TRAF6, alone (1LB4) and in complex with TRAF6-binding peptides from CD40 (1LB6) and RANK (1LB5). The crystal structure of the peptide-TRAF6 interaction revealed a TRAF6-binding motif, present also in three adaptor kinases for IL-1R/TLR signaling.