Triggering cell death: The crystal structure of Apo2L/TRAIL in a complex with death receptor 5

Formation of a complex between Apo2L (also called TRAIL) and its signaling receptors, DR4 and DR5, triggers apoptosis by inducing the oligomerization of intracellular death domains. We report the crystal structure of the comp lex between Apo2L and the ectodomain of DR5. The structure shows three elon gated receptors snuggled into long crevices between pairs of monomers of th e homotrimeric ligand. The interface is divided into two distinct patches, one near the bottom of the complex close to the receptor cell surface and o ne near the top. Both patches contain residues that are critical for high-a ffinity binding. A comparison to the structure of the lymphotoxin-receptor complex suggests general principles of binding and specificity for ligand r ecognition in the TNF receptor superfamily.