3THM
Crystal structure of Fas receptor extracellular domain in complex with Fab EP6b_B01
Summary for 3THM
| Entry DOI | 10.2210/pdb3thm/pdb |
| Related | 3TJE |
| Descriptor | Fab EP6b_B01, light chain, Fab EP6b_B01, heavy chain, Tumor necrosis factor receptor superfamily member 6, ... (6 entities in total) |
| Functional Keywords | agonistic antibody, fab fragment, antibody-receptor complex, tumor necrosis factor receptor, cysteine-rich domain, fas, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 67705.36 |
| Authors | Zuger, S.,Stirnimann, C.,Briand, C.,Grutter, M.G. (deposition date: 2011-08-19, release date: 2012-05-09, Last modification date: 2024-11-06) |
| Primary citation | Chodorge, M.,Zuger, S.,Stirnimann, C.,Briand, C.,Jermutus, L.,Grutter, M.G.,Minter, R.R. A series of Fas receptor agonist antibodies that demonstrate an inverse correlation between affinity and potency. Cell Death Differ., 19:1187-1195, 2012 Cited by PubMed Abstract: 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 Å 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. PubMed: 22261618DOI: 10.1038/cdd.2011.208 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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