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A docking model of key components of the DISC complex: death domain superfamily interactions redefined
Author(s) -
Weber Christian H,
Vincenz Claudius
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02162-7
Subject(s) - fadd , death domain , microbiology and biotechnology , docking (animal) , signal transduction , biology , apoptosis , programmed cell death , mutagenesis , regulator , caspase , chemistry , mutation , genetics , medicine , nursing , gene
Apoptosis is mediated by a highly regulated signal transduction cascade that eventually leads to precisely directed cell death. The death‐inducing signaling complex (DISC), composed of Fas, FADD, and caspase‐8, is an apical signaling complex that mediates receptor‐induced apoptosis. We have docked the experimentally determined structures of the Fas and FADD death domains into a model of a partial DISC signaling complex. The arrangement of Fas and FADD was determined using the interaction modes of the two heterodimer crystal structures determined to date, Pelle/Tube and Apaf‐1/procaspase‐9. The proposed model reveals that both interactions can be accommodated in a single multimeric complex. Importantly, the model is consistent with reported site‐directed mutagenesis data indicating residues throughout the domain are critical for function. These results imply that members of the death domain superfamily have the potential for multivalent interactions, offering novel possibilities for regulation of apoptotic signaling.