|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of a Cytokine Receptor Complex== | | ==Structure of a Cytokine Receptor Complex== |
| - | <StructureSection load='4nkq' size='340' side='right' caption='[[4nkq]], [[Resolution|resolution]] 3.30Å' scene=''> | + | <StructureSection load='4nkq' size='340' side='right'caption='[[4nkq]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4nkq]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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> | + | <table><tr><td colspan='2'>[[4nkq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/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> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4nkq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nkq OCA], [https://pdbe.org/4nkq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nkq RCSB], [https://www.ebi.ac.uk/pdbsum/4nkq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nkq ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cxe|3cxe]]</td></tr>
| + | |
| - | <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 HUMAN]), CSF2, GMCSF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CSF2RA, CSF2R, CSF2RY ([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=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], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nkq ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == 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> | + | [https://www.uniprot.org/uniprot/IL3RB_HUMAN IL3RB_HUMAN] Defects in CSF2RB are the cause of pulmonary surfactant metabolism dysfunction type 5 (SMDP5) [MIM:[https://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> |
| | == Function == | | == 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. | + | [https://www.uniprot.org/uniprot/IL3RB_HUMAN IL3RB_HUMAN] High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 20: |
| | </div> | | </div> |
| | <div class="pdbe-citations 4nkq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4nkq" 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: Parker, M W]] | + | [[Category: Broughton SE]] |
| - | [[Category: Cytokine]] | + | [[Category: Parker MW]] |
| - | [[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]]
| + | |
| Structural highlights
Disease
IL3RB_HUMAN Defects in CSF2RB are the cause of pulmonary surfactant metabolism dysfunction type 5 (SMDP5) [MIM: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.[1]
Function
IL3RB_HUMAN High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tanaka T, Motoi N, Tsuchihashi Y, Tazawa R, Kaneko C, Nei T, Yamamoto T, Hayashi T, Tagawa T, Nagayasu T, Kuribayashi F, Ariyoshi K, Nakata K, Morimoto K. Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB. J Med Genet. 2011 Mar;48(3):205-9. doi: 10.1136/jmg.2010.082586. Epub 2010 Nov, 12. PMID:21075760 doi:10.1136/jmg.2010.082586
- ↑ 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
|
