1ddf

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[[Image:1ddf.gif|left|200px]]
 
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{{Structure
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==FAS DEATH DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE==
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|PDB= 1ddf |SIZE=350|CAPTION= <scene name='initialview01'>1ddf</scene>
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<StructureSection load='1ddf' size='340' side='right'caption='[[1ddf]]' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[1ddf]] 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=1DDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DDF FirstGlance]. <br>
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|ACTIVITY=
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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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|GENE=
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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=1ddf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ddf OCA], [https://pdbe.org/1ddf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ddf RCSB], [https://www.ebi.ac.uk/pdbsum/1ddf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ddf ProSAT]</span></td></tr>
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}}
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</table>
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== Disease ==
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'''FAS DEATH DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE'''
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[https://www.uniprot.org/uniprot/TNR6_HUMAN TNR6_HUMAN] Defects in FAS are the cause of autoimmune lymphoproliferative syndrome type 1A (ALPS1A) [MIM:[https://omim.org/entry/601859 601859]; also known as Canale-Smith syndrome (CSS). ALPS is a childhood syndrome involving hemolytic anemia and thrombocytopenia with massive lymphadenopathy and splenomegaly.<ref>PMID:17336828</ref> <ref>PMID:7540117</ref> <ref>PMID:8929361</ref> <ref>PMID:9028321</ref> <ref>PMID:9028957</ref> <ref>PMID:9322534</ref> <ref>PMID:9821419</ref> <ref>PMID:10090885</ref> <ref>PMID:10515860</ref> <ref>PMID:10340403</ref> <ref>PMID:9927496</ref> <ref>PMID:11418480</ref> <ref>PMID:20935634</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/TNR6_HUMAN TNR6_HUMAN] Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro).<ref>PMID:7533181</ref> <ref>PMID:19118384</ref>
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==Overview==
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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/dd/1ddf_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=1ddf 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 ==
Programmed cell death (apoptosis) mediated by the cytokine receptor Fas is critical for the removal of autoreactive T cells, the mechanism of immune privilege, and for maintenance of immune-system homeostasis. Signalling of programmed cell death involves the self-association of a conserved cytoplasmic region of Fas called the death domain and interaction with another death-domain-containing protein, FADD (also known as MORT1). Although death domains are found in several proteins, their three-dimensional structure and the manner in which they interact is unknown. Here we describe the solution structure of the Fas death domain, as determined by NMR spectroscopy. The structure consists of six antiparallel, amphipathic alpha-helices arranged in a novel fold. From the structure and from site-directed mutagenesis, we have identified the region of the death domain involved in self-association and binding to the downstream signalling partner FADD.
Programmed cell death (apoptosis) mediated by the cytokine receptor Fas is critical for the removal of autoreactive T cells, the mechanism of immune privilege, and for maintenance of immune-system homeostasis. Signalling of programmed cell death involves the self-association of a conserved cytoplasmic region of Fas called the death domain and interaction with another death-domain-containing protein, FADD (also known as MORT1). Although death domains are found in several proteins, their three-dimensional structure and the manner in which they interact is unknown. Here we describe the solution structure of the Fas death domain, as determined by NMR spectroscopy. The structure consists of six antiparallel, amphipathic alpha-helices arranged in a novel fold. From the structure and from site-directed mutagenesis, we have identified the region of the death domain involved in self-association and binding to the downstream signalling partner FADD.
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==Disease==
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NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain.,Huang B, Eberstadt M, Olejniczak ET, Meadows RP, Fesik SW Nature. 1996 Dec 19-26;384(6610):638-41. PMID:8967952<ref>PMID:8967952</ref>
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Known diseases associated with this structure: Autoimmune lymphoproliferative syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637 134637]], Autoimmune lymphoproliferative syndrome, type IA OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637 134637]], Squamous cell carcinoma, burn scar-related, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134637 134637]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1DDF is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DDF OCA].
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</div>
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<div class="pdbe-citations 1ddf" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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NMR structure and mutagenesis of the Fas (APO-1/CD95) death domain., Huang B, Eberstadt M, Olejniczak ET, Meadows RP, Fesik SW, Nature. 1996 Dec 19-26;384(6610):638-41. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8967952 8967952]
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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: Single protein]]
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[[Category: Large Structures]]
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[[Category: Eberstadt, M.]]
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[[Category: Eberstadt M]]
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[[Category: Fesik, S.]]
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[[Category: Fesik S]]
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[[Category: Huang, B.]]
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[[Category: Huang B]]
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[[Category: Meadows, R P.]]
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[[Category: Meadows RP]]
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[[Category: Olejniczak, E.]]
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[[Category: Olejniczak E]]
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[[Category: apoptosis]]
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[[Category: death domain]]
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[[Category: glycoprotein]]
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[[Category: receptor]]
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[[Category: transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:36:40 2008''
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Current revision

FAS DEATH DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE

PDB ID 1ddf

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