6MOH
Dimeric DARPin C_R3 complex with EpoR
Summary for 6MOH
| Entry DOI | 10.2210/pdb6moh/pdb |
| Descriptor | Dimeric DARPin E2C (C_R3), Erythropoietin receptor, PHOSPHATE ION, ... (5 entities in total) |
| Functional Keywords | complex, receptor, darpin, biosynthetic protein |
| Biological source | synthetic construct More |
| Total number of polymer chains | 4 |
| Total formula weight | 86076.85 |
| Authors | Jude, K.M.,Mohan, K.,Garcia, K.C. (deposition date: 2018-10-04, release date: 2019-06-05, Last modification date: 2024-11-20) |
| Primary citation | Mohan, K.,Ueda, G.,Kim, A.R.,Jude, K.M.,Fallas, J.A.,Guo, Y.,Hafer, M.,Miao, Y.,Saxton, R.A.,Piehler, J.,Sankaran, V.G.,Baker, D.,Garcia, K.C. Topological control of cytokine receptor signaling induces differential effects in hematopoiesis. Science, 364:-, 2019 Cited by PubMed Abstract: Although tunable signaling by G protein-coupled receptors can be exploited through medicinal chemistry, a comparable pharmacological approach has been lacking for the modulation of signaling through dimeric receptors, such as those for cytokines. We present a strategy to modulate cytokine receptor signaling output by use of a series of designed C2-symmetric cytokine mimetics, based on the designed ankyrin repeat protein (DARPin) scaffold, that can systematically control erythropoietin receptor (EpoR) dimerization orientation and distance between monomers. We sampled a range of EpoR geometries by varying intermonomer angle and distance, corroborated by several ligand-EpoR complex crystal structures. Across the range, we observed full, partial, and biased agonism as well as stage-selective effects on hematopoiesis. This surrogate ligand strategy opens access to pharmacological modulation of therapeutically important cytokine and growth factor receptor systems. PubMed: 31123111DOI: 10.1126/science.aav7532 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
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