^FADDDED filaments coordinate complex IIa assembly during TNF-induced apoptosis.

ABSTRACT: Extrinsic apoptosis is initiated by signaling from death receptors, leading to the assembly of RIPK1, FADD, and caspase-8 complex. Subsequently, caspase-8 forms a filamentous structure through the oligomerization of its tandem death effector domain (tDED), resulting in caspase activation and cell death. Although the DED of FADD (^FADDDED) is homologous to the tDEDs of caspase-8 (^casp8tDED) and both oligomerize to function, the functional form of ^FADDDED oligomer in extrinsic apoptosis remains unclear. Here, using cryogenic-electron microscopy, we elucidate the structure of ^FADDDED filaments comprising three helical chains assembled through three types of iterative interactions. Mutations disrupting ^FADDDED filament formation impair the

SUBMITTER: Chen Y 

PROVIDER: S-EPMC12403089 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature