View source for 3tje


==Crystal structure of Fas receptor extracellular domain in complex with Fab E09==
<StructureSection load='3tje' size='340' side='right'caption='[[3tje]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3tje]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TJE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=3tje FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tje OCA], [https://pdbe.org/3tje PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tje RCSB], [https://www.ebi.ac.uk/pdbsum/3tje PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tje ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Receptor agonism remains poorly understood at the molecular and mechanistic level. In this study, we identified a fully human anti-Fas antibody that could efficiently trigger apoptosis and therefore function as a potent agonist. Protein engineering and crystallography were used to mechanistically understand the agonistic activity of the antibody. The crystal structure of the complex was determined at 1.9 A resolution and provided insights into epitope recognition and comparisons with the natural ligand FasL (Fas ligand). When we affinity-matured the agonist antibody, we observed that, surprisingly, the higher-affinity antibodies demonstrated a significant reduction, rather than an increase, in agonist activity at the Fas receptor. We propose and experimentally demonstrate a model to explain this non-intuitive impact of affinity on agonist antibody signalling and explore the implications for the discovery of therapeutic agonists in general.Cell Death and Differentiation advance online publication, 20 January 2012; doi:10.1038/cdd.2011.208.

A series of Fas receptor agonist antibodies that demonstrate an inverse correlation between affinity and potency.,Chodorge M, Zuger S, Stirnimann C, Briand C, Jermutus L, Grutter MG, Minter RR Cell Death Differ. 2012 Jan 20. doi: 10.1038/cdd.2011.208. PMID:22261618<ref>PMID:22261618</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3tje" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Briand C]]
[[Category: Grutter MG]]
[[Category: Stirnimann C]]
[[Category: Zuger S]]