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

@article{Eberstadt1998NMRSA,
  title={NMR structure and mutagenesis of the FADD (Mort1) death-effector domain},
  author={Matthias Eberstadt and Baohua Huang and Zehan Chen and Robert P. Meadows and Shi Chung Ng and Lixin Zheng and Michael J. Lenardo and Stephen W. Fesik},
  journal={Nature},
  year={1998},
  volume={392},
  pages={941-945}
}
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 (Mort1; ref. 2) to the membrane. FADD then activates caspase 8 (ref. 3) (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… 
The three-dimensional solution structure and dynamic properties of the human FADD death domain.
TLDR
The three-dimensional solution structure and characterised the internal polypeptide dynamics of human FADD-DD are determined and a pattern of increased rates of amide proton solvent exchange in the alpha3 helix correlates with a higher degree of solvent exposure for this secondary structure element.
Structural and biochemical analysis of the death domain complex formed at the Fas receptor
TLDR
It was found that residues from many surface regions of Fas-DD are crucial for the FADD-DD interaction, which has potentially important implications for the nature of the organisation of the death domains in the death inducing signalling complex (DISC) formed at the Fas receptor.
Evidence of complex formation between FADD and c-FLIP death effector domains for the death inducing signaling complex
TLDR
Evidence is provided indicating that the death effector domain (DED) of FADD interacts directly with the deathEffector domain of human c-FLIP, and homology modeling is used to develop a molecular docking model of Fadd and c- FLIP proteins.
Homotypic FADD interactions through a conserved RXDLL motif are required for death receptor-induced apoptosis
TLDR
It is shown that FADD self-associates through a conserved RXDLL motif in the death effector domain (DED) and this suggests that lateral interactions among adapter molecules are required for death receptor apoptosis signaling and implicateSelf-association into oligomeric assemblies as a key function of death receptor adapter proteins in initiating apoptosis.
NMR structure of the apoptosis- and inflammation-related NALP1 pyrin domain.
TLDR
The structure of NALP1 PYD differs from all other known death domain superfamily structures in that the third alpha helix is replaced by a flexibly disordered loop, which appears to relate to the molecular basis of familial Mediterranean fever (FMF), a genetic disease caused by single-point mutations.
Crystal structure of MC159 reveals molecular mechanism of DISC assembly and FLIP inhibition.
TLDR
The crystal structure of a viral FLIP, MC159, is reported, which reveals a noncanonical fold of DED1, a dumbbell-shaped structure with rigidly associated DEDs and a different mode of interaction in the DD superfamily.
Full-length Fas-associated Death Domain Protein Interacts with Short Form of Cellular FLICE Inhibitory Protein
Fas-associated death domain protein (FADD) recruits and activates procaspase-8 through interactions between the death effector domains of these two proteins. Cellular FLICE-inhibitory protein
The Solution Structure of FADD Death Domain
TLDR
The interactions between the death domains of Fas and FADD analyzed by site-directed mutagenesis indicate that charged residues in helices α2 and α3 are involved in death domain interactions, and the interacting helices appear to interact in anti-parallel pattern.
Crystal structure of the death effector domains of caspase-8.
TLDR
The first crystal structure of the N-terminal tandem death effector domains (DEDs) of caspase-8 is reported, which are similar to that of the DEDs of vFLIP MC159, which is composed of two tandem deathEffector domains that closely associate with each other in a head-to-tail manner.
FADD/MORT1, a signal transducer that can promote cell death or cell growth.
  • A. Strasser, K. Newton
  • Biology, Medicine
    The international journal of biochemistry & cell biology
  • 1999
TLDR
Experiments in mice lacking FADD/MORT1 function proved that this adaptor is required for CD95- and TNF-RI-transduced cell death but is dispensable for other pathways to apoptosis.
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The solution structure of the Fas death domain, as determined by NMR spectroscopy, is described and the region of the death domain involved in self-association and binding to the downstream signalling partner FADD is identified.
FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis
TLDR
Findings suggest that FADD may play an important role in the proximal signal transduction of Fas, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8.
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TLDR
The nuclear magnetic resonance (NMR) structure of the 145 residue long p75ICD death domain may indicate a potential site of interaction with downstream targets, and unlike the death domains involved in signaling by the TNF receptor and Fas, p75 ICD does not self‐associate in solution.
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TLDR
An adaptor molecule, RAIDD, which has an unusual bipartite architecture comprising a carboxy-terminal death domain that binds to the homologous domain in RIP, indicating that the prodomain may, through homophilic interactions, determine the specificity of binding of ICE/CED-3 zymogens to regulatory adaptor molecules.
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TLDR
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TLDR
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TLDR
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TLDR
Alanine-scanning mutagenesis of TNF-R1 confirmed that many of the amino acids conserved with Fas antigen are critical for the cytotoxic signal and is likely to define a novel domain (death domain) that signals programmed cell death.
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TLDR
The characterization of an inhibitor of apoptosis is reported, designated FLIP (for FLICE-inhibitory protein), which is predominantly expressed in muscle and lymphoid tissues and may be implicated in tissue homeostasis as an important regulator of apoptotic regulation.
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