title: The structure of FADD and its mode of interaction with procaspase-8.
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.
authors.affiliation: Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, Box 42, New York, New York 10021, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Carrington
authors.forename: Cristinel
authors.initials: C
authors.lastname: Sandu
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wei
authors.forename: Justine M
authors.initials: JM
authors.lastname: Hill
authors.forename: Gaku
authors.initials: G
authors.lastname: Morisawa
authors.forename: Ted
authors.initials: T
authors.lastname: Huang
authors.forename: Evridipis
authors.initials: E
authors.lastname: Gavathiotis
authors.forename: Yu
authors.initials: Y
authors.lastname: Wei
authors.forename: Milton H
authors.initials: MH
authors.lastname: Werner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D053181:Caspase 8; D020169:Caspases / Q000737:chemistry* / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D019169:Jurkat Cells; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014162:Transfection; D019014:fas Receptor / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases