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[[Image:2hdl.jpg|left|200px]]
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{{STRUCTURE_2hdl|  PDB=2hdl  |  SCENE=  }}
'''Solution structure of Brak/CXCL14'''


==Solution structure of Brak/CXCL14==
<StructureSection load='2hdl' size='340' side='right'caption='[[2hdl]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2hdl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HDL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HDL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=2hdl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdl OCA], [https://pdbe.org/2hdl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hdl RCSB], [https://www.ebi.ac.uk/pdbsum/2hdl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hdl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CXL14_HUMAN CXL14_HUMAN] Potent chemoattractant for neutrophils, and weaker for dendritic cells. Not chemotactic for T-cells, B-cells, monocytes, natural killer cells or granulocytes. Does not inhibit proliferation of myeloid progenitors in colony formation assays.<ref>PMID:10049774</ref> <ref>PMID:10946286</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/hd/2hdl_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2hdl ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The chemokine CXCL14/BRAK participates in immune surveillance by recruiting dendritic cells. CXCL14 gene expression is altered in a number of cancers, but protein expression levels have not been investigated. Here we report that CXCL14 protein can be expressed in primary epithelial cells; however, in several immortalized and cancer cell lines this protein is targeted for polyubiquitylation and proteasomal degradation. We determined the NMR structure of CXCL14 to identify motifs controlling its expression. CXCL14 adopts the canonical chemokine tertiary fold but contains a unique five amino acid insertion (41VSRYR45) relative to other CXC chemokines. Deletion or substitution of key residues within this insertion prevented proteasomal degradation. Furthermore, we defined a 15 amino acid fragment of CXCL14 that is sufficient to induce proteasomal degradation. This study elucidates a post-translational mechanism for the loss of CXCL14 in cancer and a novel mode of chemokine regulation.


==Overview==
Structural determinants involved in the regulation of CXCL14/BRAK expression by the 26 S proteasome.,Peterson FC, Thorpe JA, Harder AG, Volkman BF, Schwarze SR J Mol Biol. 2006 Nov 3;363(4):813-22. Epub 2006 Aug 26. PMID:16987528<ref>PMID:16987528</ref>
The chemokine CXCL14/BRAK participates in immune surveillance by recruiting dendritic cells. CXCL14 gene expression is altered in a number of cancers, but protein expression levels have not been investigated. Here we report that CXCL14 protein can be expressed in primary epithelial cells; however, in several immortalized and cancer cell lines this protein is targeted for polyubiquitylation and proteasomal degradation. We determined the NMR structure of CXCL14 to identify motifs controlling its expression. CXCL14 adopts the canonical chemokine tertiary fold but contains a unique five amino acid insertion (41VSRYR45) relative to other CXC chemokines. Deletion or substitution of key residues within this insertion prevented proteasomal degradation. Furthermore, we defined a 15 amino acid fragment of CXCL14 that is sufficient to induce proteasomal degradation. This study elucidates a post-translational mechanism for the loss of CXCL14 in cancer and a novel mode of chemokine regulation.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2HDL is a [[Single protein]] structure of 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=2HDL OCA].
</div>
<div class="pdbe-citations 2hdl" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural determinants involved in the regulation of CXCL14/BRAK expression by the 26 S proteasome., Peterson FC, Thorpe JA, Harder AG, Volkman BF, Schwarze SR, J Mol Biol. 2006 Nov 3;363(4):813-22. Epub 2006 Aug 26. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16987528 16987528]
*[[C-X-C motif chemokine 3D structures|C-X-C motif chemokine 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Harder, A G.]]
[[Category: Harder AG]]
[[Category: Peterson, F C.]]
[[Category: Peterson FC]]
[[Category: Schwarze, S R.]]
[[Category: Schwarze SR]]
[[Category: Thorpe, J A.]]
[[Category: Thorpe JA]]
[[Category: Volkman, B F.]]
[[Category: Volkman BF]]
[[Category: Brak]]
[[Category: Chemokine]]
[[Category: Cxcl14]]
[[Category: Nmr]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 06:09:23 2008''

Latest revision as of 09:10, 6 November 2024

Solution structure of Brak/CXCL14

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