1cn4: Difference between revisions
New page: left|200px<br /> <applet load="1cn4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cn4, resolution 2.800Å" /> '''ERYTHROPOIETIN COM... |
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[[Image:1cn4.gif|left|200px]]<br /> | [[Image:1cn4.gif|left|200px]]<br /><applet load="1cn4" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1cn4, resolution 2.800Å" /> | caption="1cn4, resolution 2.800Å" /> | ||
'''ERYTHROPOIETIN COMPLEXED WITH EXTRACELLULAR DOMAINS OF ERYTHROPOIETIN RECEPTOR'''<br /> | '''ERYTHROPOIETIN COMPLEXED WITH EXTRACELLULAR DOMAINS OF ERYTHROPOIETIN RECEPTOR'''<br /> | ||
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==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
1CN4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure superseeds the now removed PDB entry 1BLW. Full crystallographic information is available from [http:// | 1CN4 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure superseeds the now removed PDB entry 1BLW. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CN4 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: haematopoietic cytokine]] | [[Category: haematopoietic cytokine]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:05:34 2008'' | ||
Revision as of 15:05, 23 January 2008
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ERYTHROPOIETIN COMPLEXED WITH EXTRACELLULAR DOMAINS OF ERYTHROPOIETIN RECEPTOR
OverviewOverview
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.
About this StructureAbout this Structure
1CN4 is a Protein complex structure of sequences from Homo sapiens. This structure superseeds the now removed PDB entry 1BLW. Full crystallographic information is available from OCA.
ReferenceReference
Efficiency of signalling through cytokine receptors depends critically on receptor orientation., Syed RS, Reid SW, Li C, Cheetham JC, Aoki KH, Liu B, Zhan H, Osslund TD, Chirino AJ, Zhang J, Finer-Moore J, Elliott S, Sitney K, Katz BA, Matthews DJ, Wendoloski JJ, Egrie J, Stroud RM, Nature. 1998 Oct 1;395(6701):511-6. PMID:9774108
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