2H9G
Crystal structure of phage derived Fab BdF1 with human Death Receptor 5 (DR5)
Summary for 2H9G
| Entry DOI | 10.2210/pdb2h9g/pdb |
| Related | 1Za3 1d0g |
| Descriptor | Fab BdF1, light chain, Fab BdF1, heavy chain, Tumor necrosis factor receptor superfamily member 10B precursor, ... (4 entities in total) |
| Functional Keywords | phage display, protein engineering, combinatorial mutagenesis, antibody library, death receptor-5, agonists, immune system-apoptosis complex, immune system/apoptosis |
| Biological source | Homo sapiens (human) More |
| Cellular location | Membrane; Single-pass type I membrane protein: O14763 |
| Total number of polymer chains | 6 |
| Total formula weight | 124010.75 |
| Authors | Hymowitz, S.G.,Compaan, D.M. (deposition date: 2006-06-09, release date: 2006-08-08, Last modification date: 2024-11-20) |
| Primary citation | Li, B.,Russell, S.J.,Compaan, D.M.,Totpal, K.,Marsters, S.A.,Ashkenazi, A.,Cochran, A.G.,Hymowitz, S.G.,Sidhu, S.S. Activation of the Proapoptotic Death Receptor DR5 by Oligomeric Peptide and Antibody Agonists. J.Mol.Biol., 361:522-536, 2006 Cited by PubMed Abstract: 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. PubMed: 16859704DOI: 10.1016/j.jmb.2006.06.042 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.32 Å) |
Structure validation
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