6moi: Difference between revisions
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<StructureSection load='6moi' size='340' side='right'caption='[[6moi]], [[Resolution|resolution]] 2.06Å' scene=''> | <StructureSection load='6moi' size='340' side='right'caption='[[6moi]], [[Resolution|resolution]] 2.06Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6moi]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MOI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MOI FirstGlance]. <br> | <table><tr><td colspan='2'>[[6moi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MOI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MOI FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPOR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6moi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6moi OCA], [http://pdbe.org/6moi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6moi RCSB], [http://www.ebi.ac.uk/pdbsum/6moi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6moi ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6moi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6moi OCA], [http://pdbe.org/6moi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6moi RCSB], [http://www.ebi.ac.uk/pdbsum/6moi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6moi ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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</div> | </div> | ||
<div class="pdbe-citations 6moi" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6moi" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Erythropoietin receptor|Erythropoietin receptor]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Synthetic construct sequences]] | |||
[[Category: Garcia, K C]] | [[Category: Garcia, K C]] | ||
[[Category: Guo, Y]] | [[Category: Guo, Y]] | ||
Revision as of 14:01, 18 December 2019
Dimeric DARPin C_angle_R5 complex with EpoRDimeric DARPin C_angle_R5 complex with EpoR
Structural highlights
Disease[EPOR_HUMAN] Defects in EPOR are the cause of familial erythrocytosis type 1 (ECYT1) [MIM:133100]. ECYT1 is an autosomal dominant disorder characterized by increased serum red blood cell mass, elevated hemoglobin and hematocrit, hypersensitivity of erythroid progenitors to erythropoietin, erythropoietin low serum levels, and no increase in platelets nor leukocytes. It has a relatively benign course and does not progress to leukemia.[1] [2] [3] Function[EPOR_HUMAN] Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some cell types, can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase. Isoform EPOR-T acts as a dominant-negative receptor of EPOR-mediated signaling. Publication Abstract from PubMedAlthough 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. Topological control of cytokine receptor signaling induces differential effects in hematopoiesis.,Mohan K, Ueda G, Kim AR, Jude KM, Fallas JA, Guo Y, Hafer M, Miao Y, Saxton RA, Piehler J, Sankaran VG, Baker D, Garcia KC Science. 2019 May 24;364(6442). pii: 364/6442/eaav7532. doi:, 10.1126/science.aav7532. Epub 2019 May 23. PMID:31123111[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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