9NCQ

Cryo-EM structure of Fas-FADD complex

Summary for 9NCQ

• Entry DOI: 10.2210/pdb9ncq/pdb
• EMDB information: 49266
• Descriptor: Tumor necrosis factor receptor superfamily member 6, FAS-associated death domain protein (2 entities in total)
• Functional Keywords: fas, cd94, fadd, caspase, disc, apoptosis, innate immunity, helical assembly, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 133772.51

Authors

Fosuah, E.,Lin, Q.,Shen, Z.,Fu, T.M. (deposition date: 2025-02-17, release date: 2025-11-05, Last modification date: 2025-11-12)

Primary citation

Fosuah, E.,Shen, Z.,Xie, J.,Wang, C.,Lin, Q.,Fu, T.M.
Assembly and activation of the death-inducing signaling complex.
Proc.Natl.Acad.Sci.USA, 122:e2504819122-e2504819122, 2025

PubMed Abstract: The death-inducing signaling complex (DISC), comprising Fas, Fas-associated death domain (FADD), and caspase-8, initiates extrinsic apoptosis. Using cryogenic electron microscopy (cryo-EM), we show that Fas and FADD death domains (DDs) form an asymmetric 7:5 oligomer, which promotes FADD death effector domain (DED) filament formation. Structural analysis reveals that FADD DED filaments closely resemble caspase-8 tandem DED filaments, suggesting that FADD DED serves as a nucleation scaffold for caspase-8 assembly. These findings provide a mechanistic framework for how DISC assembly initiates apoptosis and amplifies signaling via higher-order oligomerization.

PubMed: 40465623
DOI: 10.1073/pnas.2504819122

Experimental method

ELECTRON MICROSCOPY (3.51 Å)