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==Disease== | ==CRYSTAL STRUCTURE OF THE HUMAN COLONY-STIMULATING FACTOR 1 (hCSF-1) CYTOKINE IN COMPLEX WITH THE VIRAL RECEPTOR BARF1== | ||
[[http://www.uniprot.org/uniprot/CSF1_HUMAN CSF1_HUMAN]] Note=Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.<ref>PMID:16337366</ref><ref>PMID:19934330</ref> | <StructureSection load='4adf' size='340' side='right' caption='[[4adf]], [[Resolution|resolution]] 4.40Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4adf]] is a 24 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebvg Ebvg] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ADF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ADF FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hmc|1hmc]]</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=4adf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4adf OCA], [http://pdbe.org/4adf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4adf RCSB], [http://www.ebi.ac.uk/pdbsum/4adf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4adf ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[[http://www.uniprot.org/uniprot/CSF1_HUMAN CSF1_HUMAN]] Note=Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.<ref>PMID:16337366</ref> <ref>PMID:19934330</ref> Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.<ref>PMID:16337366</ref> <ref>PMID:19934330</ref> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/BARF1_EBVG BARF1_EBVG]] Plays diverse functions in immunomodulation and oncogenicity, maybe by acting as a functional receptor for human CSF1. May inhibit interferon secretion from mononuclear cells. Exhibits oncogenic activity in vitro (By similarity). [[http://www.uniprot.org/uniprot/CSF1_HUMAN CSF1_HUMAN]] Cytokine that plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. 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, the regulation of bone resorption, and is required for normal bone development. Required for normal male and female fertility. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration. Plays a role in lipoprotein clearance.<ref>PMID:16337366</ref> <ref>PMID:19934330</ref> <ref>PMID:20829061</ref> <ref>PMID:20504948</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Hematopoietic human colony-stimulating factor 1 (hCSF-1) is essential for innate and adaptive immunity against viral and microbial infections and cancer. The human pathogen Epstein-Barr virus secretes the lytic-cycle protein BARF1 that neutralizes hCSF-1 to achieve immunomodulation. Here we show that BARF1 binds the dimer interface of hCSF-1 with picomolar affinity, away from the cognate receptor-binding site, to establish a long-lived complex featuring three hCSF-1 at the periphery of the BARF1 toroid. BARF1 locks dimeric hCSF-1 into an inactive conformation, rendering it unable to signal via its cognate receptor on human monocytes. This reveals a new functional role for hCSF-1 cooperativity in signaling. We propose a new viral strategy paradigm featuring an allosteric decoy receptor of the competitive type, which couples efficient sequestration and inactivation of the host growth factor to abrogate cooperative assembly of the cognate signaling complex. | |||
Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1.,Elegheert J, Bracke N, Pouliot P, Gutsche I, Shkumatov AV, Tarbouriech N, Verstraete K, Bekaert A, Burmeister WP, Svergun DI, Lambrecht BN, Vergauwen B, Savvides SN Nat Struct Mol Biol. 2012 Sep;19(9):938-47. doi: 10.1038/nsmb.2367. Epub 2012 Aug, 19. PMID:22902366<ref>PMID:22902366</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4adf" style="background-color:#fffaf0;"></div> | |||
== | == References == | ||
<references | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Human | </StructureSection> | ||
[[Category: Bracke, N | [[Category: Ebvg]] | ||
[[Category: Elegheert, J | [[Category: Human]] | ||
[[Category: Savvides, S N | [[Category: Bracke, N]] | ||
[[Category: Elegheert, J]] | |||
[[Category: Savvides, S N]] | |||
[[Category: Cytokine receptor-cytokine complex]] | [[Category: Cytokine receptor-cytokine complex]] | ||
[[Category: Cytokine/signaling]] | [[Category: Cytokine/signaling]] | ||