title: Identification of a basic surface area of the FADD death effector domain critical for apoptotic signaling.
abstract: Death effector domains (DEDs) are protein-protein interaction domains found in the death inducing signaling complex (DISC). Performing a structure-based alignment of all DED sequences we identified a region of high diversity in alpha-helix 3 and propose a classification of DEDs into class I DEDs typically containing a stretch of basic residues in the alpha-helix 3 region whereas DEDs of class II do not. Functional assays using mutants of Fas-associated death domain revealed that this basic region influences binding and recruitment of caspase-8 and cellular FLICE inhibitor protein to the DISC.
authors.affiliation: Institute of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Damir
authors.initials: D
authors.lastname: Bozic
authors.forename: Christophe
authors.initials: C
authors.lastname: Briand
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bodmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Zerbe
authors.forename: Andreas
authors.initials: A
authors.lastname: Kohl
authors.forename: Jürg
authors.initials: J
authors.lastname: Tschopp
authors.forename: Markus G
authors.initials: MG
authors.lastname: Grütter
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D047908:Intracellular Signaling Peptides and Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases