1eer

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(New page: 200px<br /> <applet load="1eer" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eer, resolution 1.90&Aring;" /> '''CRYSTAL STRUCTURE O...)
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[[Image:1eer.gif|left|200px]]<br />
 
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<applet load="1eer" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1eer, resolution 1.90&Aring;" />
 
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'''CRYSTAL STRUCTURE OF HUMAN ERYTHROPOIETIN COMPLEXED TO ITS RECEPTOR AT 1.9 ANGSTROMS'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF HUMAN ERYTHROPOIETIN COMPLEXED TO ITS RECEPTOR AT 1.9 ANGSTROMS==
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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.
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<StructureSection load='1eer' size='340' side='right'caption='[[1eer]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1eer]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EER OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EER FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1eer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eer OCA], [https://pdbe.org/1eer PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1eer RCSB], [https://www.ebi.ac.uk/pdbsum/1eer PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1eer ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/EPO_HUMAN EPO_HUMAN] Genetic variation in EPO is associated with susceptbility to microvascular complications of diabetes type 2 (MVCD2) [MIM:[https://omim.org/entry/612623 612623]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
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== Function ==
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[https://www.uniprot.org/uniprot/EPO_HUMAN EPO_HUMAN] Erythropoietin is the principal hormone involved in the regulation of erythrocyte differentiation and the maintenance of a physiological level of circulating erythrocyte mass.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ee/1eer_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1eer ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Erythremia (1) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133170 133170]], Erythrocytosis, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133171 133171]]
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*[[Erythropoietin|Erythropoietin]]
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*[[Erythropoietin receptor|Erythropoietin receptor]]
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==About this Structure==
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__TOC__
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1EER is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EER OCA].
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</StructureSection>
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==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9774108 9774108]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Li, C.]]
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[[Category: Li C]]
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[[Category: Syed, R.S.]]
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[[Category: Syed RS]]
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[[Category: complex (cytokine/receptor)]]
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[[Category: cytokine receptor class 1]]
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[[Category: erythropoietin]]
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[[Category: erythropoietin receptor]]
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[[Category: hematopoietic cytokine]]
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[[Category: signal transduction]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:42:28 2007''
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Current revision

CRYSTAL STRUCTURE OF HUMAN ERYTHROPOIETIN COMPLEXED TO ITS RECEPTOR AT 1.9 ANGSTROMS

PDB ID 1eer

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