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| | ==Crystal structure of phage derived Fab BdF1 with human Death Receptor 5 (DR5)== | | ==Crystal structure of phage derived Fab BdF1 with human Death Receptor 5 (DR5)== |
| - | <StructureSection load='2h9g' size='340' side='right' caption='[[2h9g]], [[Resolution|resolution]] 2.32Å' scene=''> | + | <StructureSection load='2h9g' size='340' side='right'caption='[[2h9g]], [[Resolution|resolution]] 2.32Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2h9g]] is a 6 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=2H9G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2H9G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2h9g]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H9G FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1d0g|1d0g]], [[1za3|1za3]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1d0g|1d0g]], [[1za3|1za3]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFRSF10B, DR5, KILLER, TRAILR2, TRICK2, ZTNFR9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TNFRSF10B, DR5, KILLER, TRAILR2, TRICK2, ZTNFR9 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <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=2h9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h9g OCA], [http://pdbe.org/2h9g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2h9g RCSB], [http://www.ebi.ac.uk/pdbsum/2h9g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2h9g 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=2h9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h9g OCA], [https://pdbe.org/2h9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h9g RCSB], [https://www.ebi.ac.uk/pdbsum/2h9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h9g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TR10B_HUMAN TR10B_HUMAN]] Defects in TNFRSF10B may be a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:[http://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck. | + | [[https://www.uniprot.org/uniprot/TR10B_HUMAN TR10B_HUMAN]] Defects in TNFRSF10B may be a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:[https://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck. |
| | == 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> | + | [[https://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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| - | *[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]] | + | *[[TRAIL|TRAIL]] |
| | + | *[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]] |
| | + | *[[3D structures of human antibody|3D structures of human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Compaan, D M]] | | [[Category: Compaan, D M]] |
| | [[Category: Hymowitz, S G]] | | [[Category: Hymowitz, S G]] |
| Structural highlights
2h9g is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | |
| Gene: | TNFRSF10B, DR5, KILLER, TRAILR2, TRICK2, ZTNFR9 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[TR10B_HUMAN] Defects in TNFRSF10B may be a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:275355]; also known as squamous cell carcinoma of the head and neck.
Function
[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.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The cell-extrinsic apoptotic pathway triggers programmed cell death in response to certain ligands that bind to cell-surface death receptors. Apoptosis is essential for normal development and homeostasis in metazoans, and furthermore, selective activation of the cell-extrinsic pathway in tumor cells holds considerable promise for cancer therapy. We used phage display to identify peptides and synthetic antibodies that specifically bind to the human proapoptotic death receptor DR5. Despite great differences in overall size and structure, the DR5-binding peptides and antibodies shared a tripeptide motif, which was conserved within a disulfide-constrained loop of the peptides and the third complementarity determining region of the antibody heavy chains. The X-ray crystal structure of an antibody in complex with DR5 revealed that the tripeptide motif is buried at the core of the interface, confirming its central role in antigen recognition. We found that certain peptides and antibodies exhibited potent proapoptotic activity against DR5-expressing SK-MES-1 lung carcinoma cells. These phage-derived ligands may be useful for elucidating DR5 activation at the molecular level and for creating synthetic agonists of proapoptotic death receptors.
Activation of the proapoptotic death receptor DR5 by oligomeric peptide and antibody agonists.,Li B, Russell SJ, Compaan DM, Totpal K, Marsters SA, Ashkenazi A, Cochran AG, Hymowitz SG, Sidhu SS J Mol Biol. 2006 Aug 18;361(3):522-36. Epub 2006 Jul 7. PMID:16859704[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yamaguchi H, Wang HG. CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J Biol Chem. 2004 Oct 29;279(44):45495-502. Epub 2004 Aug 18. PMID:15322075 doi:10.1074/jbc.M406933200
- ↑ Li B, Russell SJ, Compaan DM, Totpal K, Marsters SA, Ashkenazi A, Cochran AG, Hymowitz SG, Sidhu SS. Activation of the proapoptotic death receptor DR5 by oligomeric peptide and antibody agonists. J Mol Biol. 2006 Aug 18;361(3):522-36. Epub 2006 Jul 7. PMID:16859704 doi:10.1016/j.jmb.2006.06.042
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