4nkq

From Proteopedia

(Difference between revisions)

Revision as of 15:10, 16 November 2017

Structure of a Cytokine Receptor Complex

Structural highlights

4nkq is a 3 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 3cxe. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	3cxe
Gene:	CSF2RB, IL3RB, IL5RB (HUMAN), CSF2, GMCSF (HUMAN), CSF2RA, CSF2R, CSF2RY (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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] [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.^[2] ^[3]

Function

[IL3RB_HUMAN] High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor. [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. [CSF2_HUMAN] Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ 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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nkq"

@@ Line 3: / Line 3: @@
 <StructureSection load='4nkq' size='340' side='right' caption='[[4nkq]], [[Resolution|resolution]] 3.30&Aring;' 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>
+<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>
 </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='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>
@@ Line 26: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Broughton, S E]]
 [[Category: Parker, M W]]

4nkq

From Proteopedia

Revision as of 15:10, 16 November 2017

Structure of a Cytokine Receptor Complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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