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

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 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.