3oq9: Difference between revisions

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<StructureSection load='3oq9' size='340' side='right'caption='[[3oq9]], [[Resolution|resolution]] 6.80&Aring;' scene=''>
<StructureSection load='3oq9' size='340' side='right'caption='[[3oq9]], [[Resolution|resolution]] 6.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3oq9]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OQ9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[3oq9]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OQ9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OQ9 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Fas, Apt1, Tnfrsf6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), FADD, MORT1, GIG3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 6.8&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3oq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oq9 OCA], [https://pdbe.org/3oq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oq9 RCSB], [https://www.ebi.ac.uk/pdbsum/3oq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oq9 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3oq9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oq9 OCA], [https://pdbe.org/3oq9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oq9 RCSB], [https://www.ebi.ac.uk/pdbsum/3oq9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oq9 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[https://www.uniprot.org/uniprot/TNR6_MOUSE TNR6_MOUSE]] Note=Defects in Fas are the cause of the lymphoproliferation phenotype (lpr). Lpr mice show lymphadenopathy and autoantibody production. [[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> 
[https://www.uniprot.org/uniprot/TNR6_MOUSE TNR6_MOUSE] Note=Defects in Fas are the cause of the lymphoproliferation phenotype (lpr). Lpr mice show lymphadenopathy and autoantibody production.
== Function ==
== Function ==
[[https://www.uniprot.org/uniprot/TNR6_MOUSE TNR6_MOUSE]] 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 (By similarity). [[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> 
[https://www.uniprot.org/uniprot/TNR6_MOUSE TNR6_MOUSE] 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 (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The death-inducing signaling complex (DISC) formed by the death receptor Fas, the adaptor protein FADD and caspase-8 mediates the extrinsic apoptotic program. Mutations in Fas that disrupt the DISC cause autoimmune lymphoproliferative syndrome (ALPS). Here we show that the Fas-FADD death domain (DD) complex forms an asymmetric oligomeric structure composed of 5-7 Fas DD and 5 FADD DD, whose interfaces harbor ALPS-associated mutations. Structure-based mutations disrupt the Fas-FADD interaction in vitro and in living cells; the severity of a mutation correlates with the number of occurrences of a particular interaction in the structure. The highly oligomeric structure explains the requirement for hexameric or membrane-bound FasL in Fas signaling. It also predicts strong dominant negative effects from Fas mutations, which are confirmed by signaling assays. The structure optimally positions the FADD death effector domain (DED) to interact with the caspase-8 DED for caspase recruitment and higher-order aggregation.
 
The Fas-FADD death domain complex structure reveals the basis of DISC assembly and disease mutations.,Wang L, Yang JK, Kabaleeswaran V, Rice AJ, Cruz AC, Park AY, Yin Q, Damko E, Jang SB, Raunser S, Robinson CV, Siegel RM, Walz T, Wu H Nat Struct Mol Biol. 2010 Nov;17(11):1324-9. Epub 2010 Oct 10. PMID:20935634<ref>PMID:20935634</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3oq9" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Mus musculus]]
[[Category: Kabaleeswaran, V]]
[[Category: Kabaleeswaran V]]
[[Category: Wu, H]]
[[Category: Wu H]]
[[Category: Apoptosis]]
[[Category: Disc]]
[[Category: Fa]]
[[Category: Fadd]]

Latest revision as of 13:35, 21 February 2024

Structure of the FAS/FADD death domain assemblyStructure of the FAS/FADD death domain assembly

Structural highlights

3oq9 is a 10 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 6.8Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TNR6_MOUSE Note=Defects in Fas are the cause of the lymphoproliferation phenotype (lpr). Lpr mice show lymphadenopathy and autoantibody production.

Function

TNR6_MOUSE 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 (By similarity).

See Also

3oq9, resolution 6.80Å

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