Tumor necrosis factor receptors (TNFR) signal events in immune responses, Ig class switching, activation of NF-kappaB or regulation of apoptosis. TNFR-associated factors (TRAFs) are adaptor proteins that connect TNFRs to downstream signaling pathways, including the NF-kappaB and c-JUN N-terminal kinase (JNK) pathways. Members of the TRAF family exist as trimers and share a conserved TRAF domain that mediates binding to the cytoplasmic domains of TNFRs. The TRAF domain from TRAF3 has been crystallized. In addition, an N-terminally truncated form of the domain has been crystallized in space group P321 with a shortened c axis and markedly improved diffraction (2.5 A resolution).