Nature. 1998 Apr 30;392(6679):941-5.

NMR structure and mutagenesis of the FADD (Mort1) death-effector domain.External

Eberstadt, M., Huang, B., Chen, Z., Meadows, R. P., Ng, S. C., Zheng, L., Lenardo, M. J., Fesik, S. W.,
--- - Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
When activated, membrane-bound receptors for Fas and tumour-necrosis factor initiate programmed cell death by recruiting the death domain of the adaptor protein FADD to the membrane. FADD then activates caspase 8 (also known as FLICE or MACH) through an interaction between the death-effector domains of FADD and caspase 8. This ultimately leads to the apoptotic response. Death-effector domains and homologous protein modules known as caspase-recruitment domains have been found in several proteins and are important regulators of caspase (FLICE) activity and of apoptosis. Here we describe the solution structure of a soluble, biologically active mutant of the FADD death-effector domain. The structure consists of six antiparallel, amphipathic alpha-helices and resembles the overall fold of the death domains of Fas and p75. Despite this structural similarity, mutations that inhibit protein-protein interactions involving the Fas death domain have no effect when introduced into the FADD death-effector domain. Instead, a hydrophobic region of the FADD death-effector domain that is not present in the death domains is vital for binding to FLICE and for apoptotic activity.
PMID: 9582077External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DED Caspase8 Link FADD Co-immunoprecipitation T47D Not specified Not specified Human Not specified 9582077
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
Characterization
  Stoichiometry Affinity Protein-Protein interface Reference
Family DD1 DD2 Method Mutation Complex structure
DED Caspase8 Link FADD Co-immunoprecipitation F25G, F35V (FADD) 9582077
(Link: click this icon to show interactions only between the two corresponding DDs)