4nkq
From Proteopedia
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| - | ''' | + | ==Structure of a Cytokine Receptor Complex== |
| + | <StructureSection load='4nkq' size='340' side='right' caption='[[4nkq]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4nkq]] is a 3 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3cxe 3cxe]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NKQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NKQ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <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> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cxe|3cxe]]</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=4nkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nkq OCA], [http://pdbe.org/4nkq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nkq RCSB], [http://www.ebi.ac.uk/pdbsum/4nkq PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[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> | ||
| + | == Function == | ||
| + | [[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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | The | + | 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> |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 4nkq" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Broughton, S E]] | ||
| + | [[Category: Parker, M W]] | ||
| + | [[Category: Cytokine]] | ||
| + | [[Category: Cytokine-cytokine receptor complex]] | ||
| + | [[Category: Disease mutation]] | ||
| + | [[Category: Dodecamer]] | ||
| + | [[Category: Glycoprotein]] | ||
| + | [[Category: Gm-csf]] | ||
| + | [[Category: Growth factor]] | ||
| + | [[Category: Membrane]] | ||
| + | [[Category: Phosphoprotein]] | ||
| + | [[Category: Receptor complex]] | ||
| + | [[Category: Secreted]] | ||
| + | [[Category: Transmembrane]] | ||
Revision as of 14:29, 30 September 2015
Structure of a Cytokine Receptor Complex
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