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3x3f

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==TRAIL-R2 Extracellular Region Complexed to a Fab fragment from Human Agonist Antibody KMTR2==
==TRAIL-R2 Extracellular Region Complexed to a Fab fragment from Human Agonist Antibody KMTR2==
<StructureSection load='3x3f' size='340' side='right' caption='[[3x3f]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='3x3f' size='340' side='right' caption='[[3x3f]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3x3f]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3X3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3X3F FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3x3f]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3X3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3X3F FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3x3g|3x3g]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3x3g|3x3g]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3x3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3x3f OCA], [http://pdbe.org/3x3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3x3f RCSB], [http://www.ebi.ac.uk/pdbsum/3x3f PDBsum]</span></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DR5, KILLER, TNFRSF10B, TRAILR2, TRICK2, UNQ160/PRO186, ZTNFR9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3x3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3x3f OCA], [http://pdbe.org/3x3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3x3f RCSB], [http://www.ebi.ac.uk/pdbsum/3x3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3x3f ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/TR10B_HUMAN TR10B_HUMAN]] Receptor for the cytotoxic ligand TNFSF10/TRAIL. 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. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis.<ref>PMID:15322075</ref>
[[http://www.uniprot.org/uniprot/TR10B_HUMAN TR10B_HUMAN]] Receptor for the cytotoxic ligand TNFSF10/TRAIL. 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. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis.<ref>PMID:15322075</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The fully human monoclonal antibody KMTR2 acts as a strong direct agonist for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2 (TRAIL-R2), which is capable of inducing apoptotic cell death without cross-linking. To investigate the mechanism of direct agonistic activity induced by KMTR2, the crystal structure of the extracellular region of TRAIL-R2 and a Fab fragment derived from KMTR2 (KMTR2-Fab) was determined to 2.1 A resolution. Two KMTR2-Fabs assembled with the complementarity-determining region 2 of the light chain via two-fold crystallographic symmetry, suggesting that the KMTR2-Fab assembly tended to enhance TRAIL-R2 oligomerization. A single mutation at Asn53 to Arg located at the two-fold interface in the KMTR2 resulted in a loss of its apoptotic activity, although it retained its antigen-binding activity. These results indicate that the strong agonistic activity, such as apoptotic signaling and tumor regression, induced by KMTR2 is attributed to TRAIL-R2 superoligomerization induced by the interdimerization of KMTR2.
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TRAIL-R2 Superoligomerization Induced by Human Monoclonal Agonistic Antibody KMTR2.,Tamada T, Shinmi D, Ikeda M, Yonezawa Y, Kataoka S, Kuroki R, Mori E, Motoki K Sci Rep. 2015 Dec 17;5:17936. doi: 10.1038/srep17936. PMID:26672965<ref>PMID:26672965</ref>
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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 3x3f" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
[[Category: Tamada, T]]
[[Category: Tamada, T]]
[[Category: Agonist antibody]]
[[Category: Agonist antibody]]
[[Category: Apoptosis-immune system complex]]
[[Category: Apoptosis-immune system complex]]
[[Category: Trail-r2]]
[[Category: Trail-r2]]

Revision as of 08:18, 17 October 2018

TRAIL-R2 Extracellular Region Complexed to a Fab fragment from Human Agonist Antibody KMTR2

3x3f, resolution 2.10Å

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