The structural basis for the recognition of diverse receptor sequences by TRAF2

Many members of the tumor necrosis factor receptor (TNFR) superfamily initi ate intracellular signaling by recruiting TNFR-associated factors (TRAFs) t hrough their cytoplasmic tails. TRAFs apparently recognize highly diverse r eceptor sequences. crystal structures of the TRAF domain of human TRAF2 in complex with peptides from the TNFR family members CD40, CD30, Ox40, 4-1BB, and the EBV oncoprotein LMP1 revealed a conserved binding mode. A major TR AF2-binding consensus sequence, (P/S/A/T)x(Q/E)E, and a minor consensus mot if, PxQxxD, can be defined from the structural analysis, which encompass al l known TRAF2-binding sequences. The structural information provides a temp late for the further dissection of receptor binding specificity of TRAF2 an d for the understanding of the complexity of TRAF-mediated signal transduct ion.