The Structure of FADD and Its Mode of Interaction with Procaspase-8

Paul E. Carrington, Cristinel Sandu, Yufeng Wei, Justine M. Hill, Gaku Morisawa, Ted Huang, Evridipis Gavathiotis, Yu Wei, Milton H. Werner

Research output: Contribution to journalArticlepeer-review

149 Scopus citations


The structure of FADD has been solved in solution, revealing that the death effector domain (DED) and death domain (DD) are aligned with one another in an orthogonal, tail-to-tail fashion. Mutagenesis of FADD and functional reconstitution with its binding partners define the interaction with the intracellular domain of CD95 and the prodomain of procaspase-8 and reveal a self-association surface necessary to form a productive complex with an activated "death receptor." The identification of a procaspase-specific binding surface on the FADD DED suggests a preferential interaction with one, but not both, of the DEDs of procaspase-8 in a perpendicular arrangement. FADD self-association is mediated by a "hydrophobic patch" in the vicinity of F25 in the DED. The structure of FADD and its functional characterization, therefore, illustrate the architecture of key components in the death-inducing signaling complex.

Original languageEnglish (US)
Pages (from-to)599-610
Number of pages12
JournalMolecular Cell
Issue number5
StatePublished - Jun 9 2006
Externally publishedYes



ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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