Assembly of platforms for signal transduction in the new era: dimerization, helical filament assembly, and beyond

Supramolecular organizing center (SMOC)-mediated signal transduction is an emerging concept in the field of signal transduction that is ushering in a new era. The formation of location-specific, higher-order SMOCs is particularly important for cell death and innate immune signaling processes. Several protein interaction domains, including the death domain (DD) superfamily and the CIDE domain, are representative mediators of SMOC assembly in cell death and innate immune signaling pathways. DD superfamily- and CIDE domain-containing proteins form SMOCs that activate various caspases and provide signaling scaffold platforms. These assemblies can lead to signal transduction and amplification during signaling events. In this review, we summarize recent findings on the molecular basis of DD superfamily- and CIDE domain-mediated SMOC formation. Improved understanding of large molecular signaling complexes that form during innate (nonspecific) immune responses could help develop treatments for multiple diseases including cancer. Correct cell signaling requires precise protein interactions and binding, which are mediated by specific sites on the surface of the protein molecules involved. Innate immune responses and cell death mechanisms rely on such protein interactions, and defects can cause signaling abnormalities and trigger disease. Hyun Ho Park and co-workers at Chung-Ang University in Seoul, South Korea, reviewed recent insights into the presence of supramolecular organizing centers (SMOCs), localized complexes of signaling proteins that form during immune responses. The researchers highlight existing understanding of SMOC assembly processes. A better understanding of SMOCs will help to explain enzyme activation, signal amplification and cell signaling control mechanisms.