Summary for 1CN4
| Entry DOI | 10.2210/pdb1cn4/pdb |
| Descriptor | PROTEIN (ERYTHROPOIETIN RECEPTOR), PROTEIN (ERYTHROPOIETIN) (3 entities in total) |
| Functional Keywords | hematopoietic cytokine, cytokine receptor |
| Biological source | Homo sapiens (human) More |
| Cellular location | Cell membrane; Single-pass type I membrane protein. Isoform EPOR-S: Secreted : P19235 Secreted: P01588 |
| Total number of polymer chains | 3 |
| Total formula weight | 69011.48 |
| Authors | Stroud, R.M.,Reid, S.W. (deposition date: 1999-05-25, release date: 1999-08-11, Last modification date: 2024-10-09) |
| Primary citation | Syed, R.S.,Reid, S.W.,Li, C.,Cheetham, J.C.,Aoki, K.H.,Liu, B.,Zhan, H.,Osslund, T.D.,Chirino, A.J.,Zhang, J.,Finer-Moore, J.,Elliott, S.,Sitney, K.,Katz, B.A.,Matthews, D.J.,Wendoloski, J.J.,Egrie, J.,Stroud, R.M. Efficiency of signalling through cytokine receptors depends critically on receptor orientation. Nature, 395:511-516, 1998 Cited by PubMed Abstract: Human erythropoietin is a haematopoietic cytokine required for the differentiation and proliferation of precursor cells into red blood cells. It activates cells by binding and orientating two cell-surface erythropoietin receptors (EPORs) which trigger an intracellular phosphorylation cascade. The half-maximal response in a cellular proliferation assay is evoked at an erythropoietin concentration of 10 pM, 10(-2) of its Kd value for erythropoietin-EPOR binding site 1 (Kd approximately equal to nM), and 10(-5) of the Kd for erythropoietin-EPOR binding site 2 (Kd approximately equal to 1 microM). Overall half-maximal binding (IC50) of cell-surface receptors is produced with approximately 0.18 nM erythropoietin, indicating that only approximately 6% of the receptors would be bound in the presence of 10 pM erythropoietin. Other effective erythropoietin-mimetic ligands that dimerize receptors can evoke the same cellular responses but much less efficiently, requiring concentrations close to their Kd values (approximately 0.1 microM). The crystal structure of erythropoietin complexed to the extracellular ligand-binding domains of the erythropoietin receptor, determined at 1.9 A from two crystal forms, shows that erythropoietin imposes a unique 120 degrees angular relationship and orientation that is responsible for optimal signalling through intracellular kinase pathways. PubMed: 9774108DOI: 10.1038/26773 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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