2hdl
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Solution structure of Brak/CXCL14
OverviewOverview
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 StructureAbout this Structure
2HDL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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