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| - | ==Structure of the GM-CSF Receptor Complex==
| + | #REDIRECT [[4nkq]] This PDB entry is obsolete and replaced by 4nkq |
| - | <StructureSection load='3cxe' size='340' side='right' caption='[[3cxe]], [[Resolution|resolution]] 3.30Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[3cxe]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CXE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CXE FirstGlance]. <br>
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| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
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| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CSF2RB, IL3RB, IL5RB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CSF2, GMCSF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CSF2RA, CSF2R, CSF2RY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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| - | <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=3cxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cxe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cxe RCSB], [http://www.ebi.ac.uk/pdbsum/3cxe PDBsum]</span></td></tr>
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| - | </table>
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| - | == Disease ==
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| - | [[http://www.uniprot.org/uniprot/IL3RB_HUMAN IL3RB_HUMAN]] Defects in CSF2RB are the cause of pulmonary surfactant metabolism dysfunction type 5 (SMDP5) [MIM:[http://omim.org/entry/614370 614370]]. SMDP5 is 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:21075760</ref> [[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>
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| - | == Function ==
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| - | [[http://www.uniprot.org/uniprot/IL3RB_HUMAN IL3RB_HUMAN]] High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor. [[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.
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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/cx/3cxe_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/chain_selection.php?pdb_ID=2ata ConSurf].
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| - | <div style="clear:both"></div>
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that controls the production and function of blood cells, is deregulated in clinical conditions such as rheumatoid arthritis and leukemia, yet offers therapeutic value for other diseases. Its receptors are heterodimers consisting of a ligand-specific alpha subunit and a betac subunit that is shared with the interleukin (IL)-3 and IL-5 receptors. How signaling is initiated remains an enigma. We report here the crystal structure of the human GM-CSF/GM-CSF receptor ternary complex and its assembly into an unexpected dodecamer or higher-order complex. Importantly, mutagenesis of the GM-CSF receptor at the dodecamer interface and functional studies reveal that dodecamer formation is required for receptor activation and signaling. This unusual form of receptor assembly likely applies also to IL-3 and IL-5 receptors, providing a structural basis for understanding their mechanism of activation and for the development of therapeutics.
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| - | The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation.,Hansen G, Hercus TR, McClure BJ, Stomski FC, Dottore M, Powell J, Ramshaw H, Woodcock JM, Xu Y, Guthridge M, McKinstry WJ, Lopez AF, Parker MW Cell. 2008 Aug 8;134(3):496-507. PMID:18692472<ref>PMID:18692472</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Homo sapiens]]
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| - | [[Category: Hansen, G]]
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| - | [[Category: Hercus, T R]]
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| - | [[Category: Lopez, A F]]
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| - | [[Category: McClure, B J]]
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| - | [[Category: McKinstry, W J]]
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| - | [[Category: Parker, M W]]
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| - | [[Category: Stomski, F C]]
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| - | [[Category: Woodcock, J M]]
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| - | [[Category: Xu, Y]]
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| - | [[Category: Cytokine]]
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| - | [[Category: Disease mutation]]
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| - | [[Category: Dodecamer]]
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| - | [[Category: Glycoprotein]]
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| - | [[Category: Gm-csf]]
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| - | [[Category: Growth factor]]
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| - | [[Category: Membrane]]
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| - | [[Category: Phosphoprotein]]
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| - | [[Category: Receptor complex]]
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| - | [[Category: Secreted]]
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| - | [[Category: Transmembrane]]
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