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| | <StructureSection load='4y60' size='340' side='right'caption='[[4y60]], [[Resolution|resolution]] 1.75Å' scene=''> | | <StructureSection load='4y60' size='340' side='right'caption='[[4y60]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4y60]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y60 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y60 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4y60]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y60 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Sox18, Sox-18 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </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=4y60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y60 OCA], [https://pdbe.org/4y60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y60 RCSB], [https://www.ebi.ac.uk/pdbsum/4y60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y60 ProSAT]</span></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=4y60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y60 OCA], [http://pdbe.org/4y60 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y60 RCSB], [http://www.ebi.ac.uk/pdbsum/4y60 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y60 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SOX18_MOUSE SOX18_MOUSE]] Binds to the consensus sequence 5'-AACAAAG-3' and is able to trans-activate transcription via this site. | + | [https://www.uniprot.org/uniprot/SOX18_MOUSE SOX18_MOUSE] Binds to the consensus sequence 5'-AACAAAG-3' and is able to trans-activate transcription via this site. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Jauch, R]] | + | [[Category: Jauch R]] |
| - | [[Category: Kolatkar, P]] | + | [[Category: Kolatkar P]] |
| - | [[Category: Narasimhan, K]] | + | [[Category: Narasimhan K]] |
| - | [[Category: Prokoph, N]] | + | [[Category: Prokoph N]] |
| - | [[Category: Robinson, H]] | + | [[Category: Robinson H]] |
| - | [[Category: Protein-dna]]
| + | |
| - | [[Category: Sox]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| - | [[Category: Transcription-dna complex]]
| + | |
| Structural highlights
Function
SOX18_MOUSE Binds to the consensus sequence 5'-AACAAAG-3' and is able to trans-activate transcription via this site.
Publication Abstract from PubMed
The transcription factor (TF) SOX18 drives lymphatic vessel development in both embryogenesis and tumour-induced neo-lymphangiogenesis. Genetic disruption of Sox18 in a mouse model protects from tumour metastasis and established the SOX18 protein as a molecular target. Here, we report the crystal structure of the SOX18 DNA binding high-mobility group (HMG) box bound to a DNA element regulating Prox1 transcription. The crystals diffracted to 1.75A presenting the highest resolution structure of a SOX/DNA complex presently available revealing water structure, structural adjustments at the DNA contact interface and non-canonical conformations of the DNA backbone. To explore alternatives to challenging small molecule approaches for targeting the DNA-binding activity of SOX18, we designed a set of five decoys based on modified Prox1-DNA. Four decoys potently inhibited DNA binding of SOX18 in vitro and did not interact with non-SOX TFs. Serum stability, nuclease resistance and thermal denaturation assays demonstrated that a decoy circularized with a hexaethylene glycol linker and terminal phosphorothioate modifications is most stable. This SOX decoy also interfered with the expression of a luciferase reporter under control of a SOX18-dependent VCAM1 promoter in COS7 cells. Collectively, we propose SOX decoys as potential strategy for inhibiting SOX18 activity to disrupt tumour-induced neo-lymphangiogenesis.
Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction.,Klaus M, Prokoph N, Girbig M, Wang X, Huang YH, Srivastava Y, Hou L, Narasimhan K, Kolatkar PR, Francois M, Jauch R Nucleic Acids Res. 2016 May 5;44(8):3922-35. doi: 10.1093/nar/gkw130. Epub 2016, Mar 2. PMID:26939885[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Klaus M, Prokoph N, Girbig M, Wang X, Huang YH, Srivastava Y, Hou L, Narasimhan K, Kolatkar PR, Francois M, Jauch R. Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction. Nucleic Acids Res. 2016 May 5;44(8):3922-35. doi: 10.1093/nar/gkw130. Epub 2016, Mar 2. PMID:26939885 doi:http://dx.doi.org/10.1093/nar/gkw130
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