Abstract
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 language | English (US) |
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Pages (from-to) | 599-610 |
Number of pages | 12 |
Journal | Molecular Cell |
Volume | 22 |
Issue number | 5 |
DOIs | |
State | Published - Jun 9 2006 |
Externally published | Yes |
Keywords
- CELLCYCLE
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology