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| | ==Crystal structure of receptor-cytokine complex== | | ==Crystal structure of receptor-cytokine complex== |
| - | <StructureSection load='4rs1' size='340' side='right' caption='[[4rs1]], [[Resolution|resolution]] 2.68Å' scene=''> | + | <StructureSection load='4rs1' size='340' side='right'caption='[[4rs1]], [[Resolution|resolution]] 2.68Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rs1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RS1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RS1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rs1]] is a 2 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=4RS1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RS1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSF2R, CSF2RA, CSF2RY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CSF2, GMCSF ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4rs1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rs1 OCA], [https://pdbe.org/4rs1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rs1 RCSB], [https://www.ebi.ac.uk/pdbsum/4rs1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rs1 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=4rs1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rs1 OCA], [http://pdbe.org/4rs1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rs1 RCSB], [http://www.ebi.ac.uk/pdbsum/4rs1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rs1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CSF2R_HUMAN CSF2R_HUMAN]] Defects in CSF2RA are the cause of pulmonary surfactant metabolism dysfunction type 4 (SMDP4) [MIM:[http://omim.org/entry/300770 300770]]. A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.<ref>PMID:18955567</ref> <ref>PMID:18955570</ref> | + | [https://www.uniprot.org/uniprot/CSF2R_HUMAN CSF2R_HUMAN] Defects in CSF2RA are the cause of pulmonary surfactant metabolism dysfunction type 4 (SMDP4) [MIM:[https://omim.org/entry/300770 300770]. A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.<ref>PMID:18955567</ref> <ref>PMID:18955570</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CSF2R_HUMAN CSF2R_HUMAN]] Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells. [[http://www.uniprot.org/uniprot/CSF2_HUMAN CSF2_HUMAN]] Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. | + | [https://www.uniprot.org/uniprot/CSF2R_HUMAN CSF2R_HUMAN] Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4rs1" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4rs1" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Colony-stimulating factor 3D structures|Colony-stimulating factor 3D structures]] |
| | + | *[[Colony-stimulating factor receptor 3D structures|Colony-stimulating factor receptor 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Broughton, S E]] | + | [[Category: Large Structures]] |
| - | [[Category: Dhagat, U]] | + | [[Category: Broughton SE]] |
| - | [[Category: Parker, M W]] | + | [[Category: Dhagat U]] |
| - | [[Category: Cytokine]] | + | [[Category: Parker MW]] |
| - | [[Category: Cytokine receptor-cytokine complex]]
| + | |
| - | [[Category: Receptor]]
| + | |
| Structural highlights
Disease
CSF2R_HUMAN Defects in CSF2RA are the cause of pulmonary surfactant metabolism dysfunction type 4 (SMDP4) [MIM:300770. A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.[1] [2]
Function
CSF2R_HUMAN Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells.
Publication Abstract from PubMed
The GM-CSF, IL-3, and IL-5 receptors constitute the betac family, playing important roles in inflammation, autoimmunity, and cancer. Typical of heterodimeric type I cytokine receptors, signaling requires recruitment of the shared subunit to the initial cytokine:alpha subunit binary complex through an affinity conversion mechanism. This critical process is poorly understood due to the paucity of crystal structures of both binary and ternary receptor complexes for the same cytokine. We have now solved the structure of the binary GM-CSF:GMRalpha complex at 2.8-A resolution and compared it with the structure of the ternary complex, revealing distinct conformational changes. Guided by these differences we performed mutational and functional studies that, importantly, show GMRalpha interactions playing a major role in receptor signaling while betac interactions control high-affinity binding. These results support the notion that conformational changes underlie the mechanism of GM-CSF receptor activation and also suggest how related type I cytokine receptors signal.
Conformational Changes in the GM-CSF Receptor Suggest a Molecular Mechanism for Affinity Conversion and Receptor Signaling.,Broughton SE, Hercus TR, Nero TL, Dottore M, McClure BJ, Dhagat U, Taing H, Gorman MA, King-Scott J, Lopez AF, Parker MW Structure. 2016 Jul 6. pii: S0969-2126(16)30124-1. doi:, 10.1016/j.str.2016.05.017. PMID:27396825[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Martinez-Moczygemba M, Doan ML, Elidemir O, Fan LL, Cheung SW, Lei JT, Moore JP, Tavana G, Lewis LR, Zhu Y, Muzny DM, Gibbs RA, Huston DP. Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1. J Exp Med. 2008 Nov 24;205(12):2711-6. doi: 10.1084/jem.20080759. Epub 2008 Oct, 27. PMID:18955567 doi:10.1084/jem.20080759
- ↑ Suzuki T, Sakagami T, Rubin BK, Nogee LM, Wood RE, Zimmerman SL, Smolarek T, Dishop MK, Wert SE, Whitsett JA, Grabowski G, Carey BC, Stevens C, van der Loo JC, Trapnell BC. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J Exp Med. 2008 Nov 24;205(12):2703-10. doi: 10.1084/jem.20080990. Epub 2008 Oct , 27. PMID:18955570 doi:10.1084/jem.20080990
- ↑ Broughton SE, Hercus TR, Nero TL, Dottore M, McClure BJ, Dhagat U, Taing H, Gorman MA, King-Scott J, Lopez AF, Parker MW. Conformational Changes in the GM-CSF Receptor Suggest a Molecular Mechanism for Affinity Conversion and Receptor Signaling. Structure. 2016 Jul 6. pii: S0969-2126(16)30124-1. doi:, 10.1016/j.str.2016.05.017. PMID:27396825 doi:http://dx.doi.org/10.1016/j.str.2016.05.017
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