Molecular Cell
Volume 22, Issue 5, 9 June 2006, Pages 599-610
Journal home page for Molecular Cell

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

https://doi.org/10.1016/j.molcel.2006.04.018Get rights and content
Under an Elsevier user license
open archive

Summary

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.

CELLCYCLE

Cited by (0)

2

These authors contributed equally to this work.

3

Present address: Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia.