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

Abstract

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.

Macrophage aggresome-like induced structures are flexible organizing platforms for immune signaling

“…The SMOCs, which included the myddosome, the triffosome, and the inflammasomes among others, are welldescribed examples of such complexes. These SMOCs shared the properties of assembling on membranous organelles and often required proteins containing death effector domains (DEDs), pyrin domains (PYRs), or caspase activation and recruitment domains (CARDs) that nucleates helical filament formation by homotypic protein-protein interactions (Kagan et al, 2014, Ha et al, 2020). Although this model for immune signaling is attractive, the SMOCs are not unique in their function of organizing centers for immune responses.…”