Cryo-EM structural analysis of FADD: Caspase-8 complexes defines the catalytic dimer architecture for co-ordinated control of cell fate

Uncovering the molecular architecture of the core FADD:Caspase-8 complex and how this is altered by regulatory partners, such as the cell death inhibitor c-FLIP, is essential to understand co-ordination of cell fate. Here, using electron microscopy, we visualize for the first time fulllength procaspase-8 in a complex with FADD. Our structural analysis reveals how the FADDnucleated tandem death effector domain (tDED) helical filament is required to correctly orientate procaspase-8 catalytic domains, enabling activation via anti-parallel dimerization.