Structural basis of signal transduction in the TNF receptor superfamily.

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 understanding the biophysical principles in these signaling cascades.