2h9g
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= TNFRSF10B, DR5, KILLER, TRAILR2, TRICK2, ZTNFR9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= TNFRSF10B, DR5, KILLER, TRAILR2, TRICK2, ZTNFR9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1d0g|1d0g]], [[1za3|1Za3]] | ||
| + | |RESOURCES=<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://www.ebi.ac.uk/pdbsum/2h9g PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2h9g RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Squamous cell carcinoma, head and neck OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603612 603612]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: protein engineering]] | [[Category: protein engineering]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:27:17 2008'' |
Revision as of 00:27, 31 March 2008
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| , resolution 2.32Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | TNFRSF10B, DR5, KILLER, TRAILR2, TRICK2, ZTNFR9 (Homo sapiens) | ||||||
| Related: | 1d0g, 1Za3
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of phage derived Fab BdF1 with human Death Receptor 5 (DR5)
Overview
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.
About this Structure
2H9G is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 03:27:17 2008
