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{{STRUCTURE_2d9q| PDB=2d9q |  SCENE=  }}
==Crystal Structure of the Human GCSF-Receptor Signaling Complex==
===Crystal Structure of the Human GCSF-Receptor Signaling Complex===
<StructureSection load='2d9q' size='340' side='right' caption='[[2d9q]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
{{ABSTRACT_PUBMED_16492764}}
== Structural highlights ==
<table><tr><td colspan='2'>[[2d9q]] is a 2 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=2D9Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2D9Q FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2d9q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d9q OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2d9q RCSB], [http://www.ebi.ac.uk/pdbsum/2d9q PDBsum]</span></td></tr>
<table>
== Disease ==
[[http://www.uniprot.org/uniprot/CSF3R_HUMAN CSF3R_HUMAN]] Defects in CSF3R are the cause of hereditary neutrophilia (NEUTROPHILIA) [MIM:[http://omim.org/entry/162830 162830]]. A form of lifelong, persistent neutrophilia, a condition characterized by an increase in the number of neutrophils in the blood.<ref>PMID:19620628</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/CSF3_HUMAN CSF3_HUMAN]] Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes. [[http://www.uniprot.org/uniprot/CSF3R_HUMAN CSF3R_HUMAN]] Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface.<ref>PMID:7514305</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d9/2d9q_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A crystal structure of the signaling complex between human granulocyte colony-stimulating factor (GCSF) and a ligand binding region of GCSF receptor (GCSF-R), has been determined to 2.8 A resolution. The GCSF:GCSF-R complex formed a 2:2 stoichiometry by means of a cross-over interaction between the Ig-like domains of GCSF-R and GCSF. The conformation of the complex is quite different from that between human GCSF and the cytokine receptor homologous domain of mouse GCSF-R, but similar to that of the IL-6/gp130 signaling complex. The Ig-like domain cross-over structure necessary for GCSF-R activation is consistent with previously reported thermodynamic and mutational analyses.


==Disease==
Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex.,Tamada T, Honjo E, Maeda Y, Okamoto T, Ishibashi M, Tokunaga M, Kuroki R Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3135-40. Epub 2006 Feb 21. PMID:16492764<ref>PMID:16492764</ref>
[[http://www.uniprot.org/uniprot/CSF3R_HUMAN CSF3R_HUMAN]] Defects in CSF3R are the cause of hereditary neutrophilia (NEUTROPHILIA) [MIM:[http://omim.org/entry/162830 162830]]. A form of lifelong, persistent neutrophilia, a condition characterized by an increase in the number of neutrophils in the blood.<ref>PMID:19620628</ref>  


==Function==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[http://www.uniprot.org/uniprot/CSF3_HUMAN CSF3_HUMAN]] Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes. [[http://www.uniprot.org/uniprot/CSF3R_HUMAN CSF3R_HUMAN]] Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface.<ref>PMID:7514305</ref>  
</div>
 
== References ==
==About this Structure==
<references/>
[[2d9q]] is a 2 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=2D9Q OCA].
__TOC__
 
</StructureSection>
==Reference==
<ref group="xtra">PMID:016492764</ref><ref group="xtra">PMID:014992583</ref><references group="xtra"/><references/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Kuroki, R.]]
[[Category: Kuroki, R.]]

Revision as of 12:59, 3 October 2014

Crystal Structure of the Human GCSF-Receptor Signaling ComplexCrystal Structure of the Human GCSF-Receptor Signaling Complex

Structural highlights

2d9q is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, RCSB, PDBsum

Disease

[CSF3R_HUMAN] Defects in CSF3R are the cause of hereditary neutrophilia (NEUTROPHILIA) [MIM:162830]. A form of lifelong, persistent neutrophilia, a condition characterized by an increase in the number of neutrophils in the blood.[1]

Function

[CSF3_HUMAN] Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages. This CSF induces granulocytes. [CSF3R_HUMAN] Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation. Plays a crucial role in the proliferation, differientation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface.[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A crystal structure of the signaling complex between human granulocyte colony-stimulating factor (GCSF) and a ligand binding region of GCSF receptor (GCSF-R), has been determined to 2.8 A resolution. The GCSF:GCSF-R complex formed a 2:2 stoichiometry by means of a cross-over interaction between the Ig-like domains of GCSF-R and GCSF. The conformation of the complex is quite different from that between human GCSF and the cytokine receptor homologous domain of mouse GCSF-R, but similar to that of the IL-6/gp130 signaling complex. The Ig-like domain cross-over structure necessary for GCSF-R activation is consistent with previously reported thermodynamic and mutational analyses.

Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex.,Tamada T, Honjo E, Maeda Y, Okamoto T, Ishibashi M, Tokunaga M, Kuroki R Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3135-40. Epub 2006 Feb 21. PMID:16492764[3]

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

References

  1. ↑ Plo I, Zhang Y, Le Couedic JP, Nakatake M, Boulet JM, Itaya M, Smith SO, Debili N, Constantinescu SN, Vainchenker W, Louache F, de Botton S. An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia. J Exp Med. 2009 Aug 3;206(8):1701-7. doi: 10.1084/jem.20090693. Epub 2009 Jul 20. PMID:19620628 doi:10.1084/jem.20090693
  2. ↑ Dong F, Hoefsloot LH, Schelen AM, Broeders CA, Meijer Y, Veerman AJ, Touw IP, Lowenberg B. Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4480-4. PMID:7514305
  3. ↑ Tamada T, Honjo E, Maeda Y, Okamoto T, Ishibashi M, Tokunaga M, Kuroki R. Homodimeric cross-over structure of the human granulocyte colony-stimulating factor (GCSF) receptor signaling complex. Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3135-40. Epub 2006 Feb 21. PMID:16492764

2d9q, resolution 2.80Å

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