Members of the tumor necrosis factor receptor superfamily play key roles in innate and
adaptive immunity. Here, we review recent structural studies in the intracellular signal
transduction of these receptors. A central theme revealed from these structural studies is that
upon ligand binding, multiple intracellular proteins form higher-order signaling machines to
transduce and amplify receptor activation information to different cellular fates, including NF-
κB activation, apoptosis, and programmed necrosis. These studies open a new vista for …