Figure 4.

Signaling by TNF superfamily receptors. Ligand-promoted trimerization (top) positions the receptor intracellular domains to match the spacing between the receptor binding sites on the TRAF2 trimer (bottom). The trimeric receptor (top) is represented by the structure of the TNF–TNF-R1–extracellular-domain complex (27). Simultaneous TRAF binding to three receptor cytoplasmic domains (bottom) increases avidity and leads to selective recognition of activated, trimeric receptors. The region between the complexes is shown at approximately half scale. Assuming unfolded segments of ≈30 aa flanking the transmembrane helix, the intracellular and extracellular complexes are expected to be ≈150 Å apart.