FADD self-association is required for stable interaction with an activated death receptor

C Sandu, G Morisawa, I Wegorzewska, T Huang, A F Arechiga, J M Hill, T Kim, C M Walsh, M H Werner
2006 Cell Death and Differentiation  
Receptor-mediated programmed cell death proceeds through an activated receptor to which the death adaptor FADD and the initiator procaspases 8 and/or 10 are recruited following receptor stimulation. The adaptor FADD is responsible for both receptor binding and recruitment of the procaspases into the death-inducing signaling complex. Biochemical dissection of the FADD death effector domain and functional replacement with a coiled-coil motif demonstrates that there is an obligatory FADD
more » ... tory FADD self-association via the DED during assembly of the death-inducing signaling complex. Using engineered oligomerization motifs with defined stoichiometries, the requirement for FADD self-association through the DED can be separated from the caspase-recruitment function of the domain. Disruption of FADD self-association precludes formation of a competent signaling complex. On this basis, we propose an alternative architecture for the FADD signaling complex in which FADD acts as a molecular bridge to stitch together an array of activated death receptors.
doi:10.1038/sj.cdd.4401966 pmid:16710361 fatcat:wkf6jqpon5gcrfezocdbu7asfi