View source for 4dkd


==Crystal Structure of Human Interleukin-34 Bound to Human CSF-1R==
<StructureSection load='4dkd' size='340' side='right'caption='[[4dkd]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4dkd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DKD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4dkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dkd OCA], [https://pdbe.org/4dkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dkd RCSB], [https://www.ebi.ac.uk/pdbsum/4dkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dkd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IL34_HUMAN IL34_HUMAN] Cytokine that promotes the proliferation, survival and differentiation of monocytes and macrophages. Promotes the release of proinflammatory chemokines, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, and in the regulation of bone resorption. Signaling via CSF1R and its downstream effectors stimulates phosphorylation of MAPK1/ERK2 AND MAPK3/ERK1.<ref>PMID:18467591</ref> <ref>PMID:20489731</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Lacking any discernible sequence similarity, interleukin-34 (IL-34) and colony stimulating factor 1 (CSF-1) signal through a common receptor CSF-1R on cells of mononuclear phagocyte lineage. Here, the crystal structure of dimeric IL-34 reveals a helical cytokine fold homologous to CSF-1, and we further show that the complex architecture of IL-34 bound to the N-terminal immunoglobulin domains of CSF-1R is similar to the CSF-1/CSF-1R assembly. However, unique conformational adaptations in the receptor domain geometry and intermolecular interface explain the cross-reactivity of CSF-1R for two such distantly related ligands. The docking adaptations of the IL-34 and CSF-1 quaternary complexes, when compared to the stem cell factor assembly, draw a common evolutionary theme for transmembrane signaling. In addition, the structure of IL-34 engaged by a Fab fragment reveals the mechanism of a neutralizing antibody that can help deconvolute IL-34 from CSF-1 biology, with implications for therapeutic intervention in diseases with myeloid pathogenic mechanisms.

Structural Basis for the Dual Recognition of Helical Cytokines IL-34 and CSF-1 by CSF-1R.,Ma X, Lin WY, Chen Y, Stawicki S, Mukhyala K, Wu Y, Martin F, Bazan JF, Starovasnik MA Structure. 2012 Apr 4;20(4):676-87. Epub 2012 Apr 3. PMID:22483114<ref>PMID:22483114</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4dkd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Colony-stimulating factor receptor 3D structures|Colony-stimulating factor receptor 3D structures]]
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bazan JF]]
[[Category: Ma X]]
[[Category: Starovasnik MA]]