Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis.

ABSTRACT: Fas-associated protein with death domain (FADD), procaspase-8, and cellular FLICE-inhibitory proteins (cFLIP) assemble through death-effector domains (DEDs), directing death receptor signaling towards cell survival or apoptosis. Understanding their three-dimensional regulatory mechanism has been limited by the absence of atomic coordinates for their ternary DED complex. By employing X-ray crystallography and cryogenic electron microscopy (cryo-EM), we present the atomic coordinates of human FADD-procaspase-8-cFLIP complexes, revealing structural insights into these critical interactions. These structures illustrate how FADD and cFLIP orchestrate the assembly of caspase-8-containing complexes and offer mechanistic explanations for their role in promoting or inhibiting apoptotic and necropto

SUBMITTER: Yang CY 

PROVIDER: S-EPMC11074299 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature