Identification of a basic surface area of the FADD death effector domain critical for apoptotic signaling

AbstractDeath 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 α-helix 3 and propose a classification of DEDs into class I DEDs typically containing a stretch of basic residues in the α-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