1e3y

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{{STRUCTURE_1e3y| PDB=1e3y | SCENE= }}
 
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===DEATH DOMAIN FROM HUMAN FADD/MORT1===
 
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{{ABSTRACT_PUBMED_10964568}}
 
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==About this Structure==
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==Death domain from human FADD/MORT1==
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[[1e3y]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E3Y OCA].
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<StructureSection load='1e3y' size='340' side='right'caption='[[1e3y]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1e3y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1E3Y FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1e3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1e3y OCA], [https://pdbe.org/1e3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1e3y RCSB], [https://www.ebi.ac.uk/pdbsum/1e3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1e3y ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/FADD_HUMAN FADD_HUMAN] Defects in FADD are the cause of infections recurrent associated with encephalopathy hepatic dysfunction and cardiovascular malformations (IEHDCM) [MIM:[https://omim.org/entry/613759 613759]. A condition with biological features of autoimmune lymphoproliferative syndrome such as high-circulating CD4(-)CD8(-)TCR-alpha-beta(+) T-cell counts, and elevated IL10 and FASL levels. Affected individuals suffer from recurrent, stereotypical episodes of fever, encephalopathy, and mild liver dysfunction sometimes accompanied by generalized seizures. The episodes can be triggered by varicella zoster virus (VZV), measles mumps rubella (MMR) attenuated vaccine, parainfluenza virus, and Epstein-Barr virus (EBV).<ref>PMID:21109225</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/FADD_HUMAN FADD_HUMAN] Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling.<ref>PMID:21109225</ref> <ref>PMID:16762833</ref> <ref>PMID:19118384</ref> <ref>PMID:20935634</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e3/1e3y_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1e3y ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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FADD (also known as MORT-1) is an essential adapter protein that couples the transmembrane receptors Fas (CD95) and tumor necrosis factor receptor-1 (TNF-R1) to intracellular cysteine proteases known as caspases, which propagate and execute the programmed cell death-inducing signal triggered by Fas ligand (FasL, CD95L) and TNF. FADD contains 208 amino acid residues, and comprises two functionally and structurally distinct domains: an N-terminal death effector domain (DED) that promotes activation of the downstream proteolytic cascade through binding of the DED domains of procaspase-8; and a C-terminal death domain (DD). FADD-DD provides the site of FADD recruitment to death receptor complexes at the plasma membrane by, for example, interaction with the Fas receptor cytoplasmic death domain (Fas-DD), or binding of the TNF-R1 adapter molecule TRADD. We have determined the three-dimensional solution structure and characterised the internal polypeptide dynamics of human FADD-DD using heteronuclear NMR spectroscopy of (15)N and (13)C,(15)N-labelled samples. The structure comprises six alpha-helices joined by short loops and displays overall similarity to the death domain of the Fas receptor. The analysis of the dynamic properties reveals no evidence of contiguous stretches of polypeptide chain with increased internal motion, except at the extreme chain termini. 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. The properties of the FADD-DD structure are discussed with respect to previously reported mutagenesis data and emerging models for FasL-induced FADD recruitment to Fas and caspase-8 activation.
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==Reference==
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The three-dimensional solution structure and dynamic properties of the human FADD death domain.,Berglund H, Olerenshaw D, Sankar A, Federwisch M, McDonald NQ, Driscoll PC J Mol Biol. 2000 Sep 8;302(1):171-88. PMID:10964568<ref>PMID:10964568</ref>
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<ref group="xtra">PMID:010964568</ref><references group="xtra"/><references/>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1e3y" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Berglund, H.]]
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[[Category: Large Structures]]
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[[Category: Driscoll, P C.]]
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[[Category: Berglund H]]
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[[Category: Mcdonald, N Q.]]
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[[Category: Driscoll PC]]
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[[Category: Olerenshaw, D.]]
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[[Category: McDonald NQ]]
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[[Category: Adapter molecule]]
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[[Category: Olerenshaw D]]
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[[Category: Apoptosis]]
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[[Category: Death domain]]
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[[Category: Fas receptor death inducing signalling complex]]
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Current revision

Death domain from human FADD/MORT1

PDB ID 1e3y

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