Journal of Biological Chemistry · 1999 · 106 citations · 42 references
Life SciencesCell BiologyMolecular BiologyApoptosisSignal TransductionStructural BiologyApoptosis RegulationApoptotic Signal TransductionApoptotic SignalingCell DeathDeath ReceptorsExtrinsic Apoptotic PathwayAlpha HelicesApoptosis Signaling PathwaysApoptotic Signaling CascadesDeath DomainsFadd-dependent SignalingFas Receptor SignalingFas-associated Death Domain ProteinProtein-protein Interactions In Apoptosis
A signal of Fas-mediated apoptosis is transferred through an adaptor protein Fas-associated death domain protein (FADD) by interactions between the death domains of Fas and FADD. To understand the signal transduction mechanism of Fas-mediated apoptosis, we solved the solution structure of a murine FADD death domain. It consists of six helices arranged in a similar fold to the other death domains. The interactions between the death domains of Fas and FADD analyzed by site-directed mutagenesis indicate that charged residues in helices alpha2 and alpha3 are involved in death domain interactions, and the interacting helices appear to interact in anti-parallel pattern, alpha2 of FADD with alpha3 of Fas and vice versa.
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