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| | ==Crystal structure of ZNF217 bound to DNA== | | ==Crystal structure of ZNF217 bound to DNA== |
| - | <StructureSection load='4is1' size='340' side='right' caption='[[4is1]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='4is1' size='340' side='right'caption='[[4is1]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4is1]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IS1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IS1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4is1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IS1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IS1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4f2j|4f2j]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ZNF217, ZABC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4is1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4is1 OCA], [https://pdbe.org/4is1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4is1 RCSB], [https://www.ebi.ac.uk/pdbsum/4is1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4is1 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=4is1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4is1 OCA], [http://pdbe.org/4is1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4is1 RCSB], [http://www.ebi.ac.uk/pdbsum/4is1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4is1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ZN217_HUMAN ZN217_HUMAN]] Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'.<ref>PMID:16203743</ref> <ref>PMID:17259635</ref> <ref>PMID:18625718</ref> <ref>PMID:16940172</ref> | + | [https://www.uniprot.org/uniprot/ZN217_HUMAN ZN217_HUMAN] Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'.<ref>PMID:16203743</ref> <ref>PMID:17259635</ref> <ref>PMID:18625718</ref> <ref>PMID:16940172</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Classical zinc fingers (ZFs) are one of the most abundant and best characterized DNA-binding domains. Typically, tandem arrays of three or more ZFs bind DNA target sequences with high affinity and specificity, and the mode of DNA recognition is sufficiently well understood that tailor-made ZF-based DNA-binding proteins can be engineered. We have shown previously that a two-zinc finger unit found in the transcriptional coregulator ZNF217 recognizes DNA but with an affinity and specificity that is lower than other ZF arrays. To investigate the basis for these differences, we determined the structure of a ZNF217-DNA complex. We show that although the overall position of the ZFs on the DNA closely resembles that observed for other ZFs, the side-chain interaction pattern differs substantially from the canonical model. The structure also reveals the presence of two methyl-pi interactions, each featuring a tyrosine contacting a thymine methyl group. To our knowledge, interactions of this type have not previously been described in classical ZF-DNA complexes. Finally, we investigated the sequence specificity of this two-ZF unit and discuss how ZNF217 might discriminate its target DNA sites in the cell. |
| | + | |
| | + | New insights into DNA recognition by zinc fingers revealed by structural analysis of the oncoprotein ZNF217.,Vandevenne M, Jacques DA, Artuz C, Nguyen CD, Kwan AH, Segal DJ, Matthews JM, Crossley M, Guss JM, Mackay JP J Biol Chem. 2013 Apr 12;288(15):10616-27. doi: 10.1074/jbc.M112.441451. Epub, 2013 Feb 22. PMID:23436653<ref>PMID:23436653</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 4is1" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Guss, J M]] | + | [[Category: Large Structures]] |
| - | [[Category: Jacques, D A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Mackay, J P]] | + | [[Category: Guss JM]] |
| - | [[Category: Vandevenne, M S]] | + | [[Category: Jacques DA]] |
| - | [[Category: Metal binding protein-dna complex]] | + | [[Category: Mackay JP]] |
| - | [[Category: Transcription factor]] | + | [[Category: Vandevenne MS]] |
| - | [[Category: Zinc finger]]
| + | |
| Structural highlights
Function
ZN217_HUMAN Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'.[1] [2] [3] [4]
Publication Abstract from PubMed
Classical zinc fingers (ZFs) are one of the most abundant and best characterized DNA-binding domains. Typically, tandem arrays of three or more ZFs bind DNA target sequences with high affinity and specificity, and the mode of DNA recognition is sufficiently well understood that tailor-made ZF-based DNA-binding proteins can be engineered. We have shown previously that a two-zinc finger unit found in the transcriptional coregulator ZNF217 recognizes DNA but with an affinity and specificity that is lower than other ZF arrays. To investigate the basis for these differences, we determined the structure of a ZNF217-DNA complex. We show that although the overall position of the ZFs on the DNA closely resembles that observed for other ZFs, the side-chain interaction pattern differs substantially from the canonical model. The structure also reveals the presence of two methyl-pi interactions, each featuring a tyrosine contacting a thymine methyl group. To our knowledge, interactions of this type have not previously been described in classical ZF-DNA complexes. Finally, we investigated the sequence specificity of this two-ZF unit and discuss how ZNF217 might discriminate its target DNA sites in the cell.
New insights into DNA recognition by zinc fingers revealed by structural analysis of the oncoprotein ZNF217.,Vandevenne M, Jacques DA, Artuz C, Nguyen CD, Kwan AH, Segal DJ, Matthews JM, Crossley M, Guss JM, Mackay JP J Biol Chem. 2013 Apr 12;288(15):10616-27. doi: 10.1074/jbc.M112.441451. Epub, 2013 Feb 22. PMID:23436653[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huang G, Krig S, Kowbel D, Xu H, Hyun B, Volik S, Feuerstein B, Mills GB, Stokoe D, Yaswen P, Collins C. ZNF217 suppresses cell death associated with chemotherapy and telomere dysfunction. Hum Mol Genet. 2005 Nov 1;14(21):3219-25. Epub 2005 Oct 3. PMID:16203743 doi:10.1093/hmg/ddi352
- ↑ Krig SR, Jin VX, Bieda MC, O'Geen H, Yaswen P, Green R, Farnham PJ. Identification of genes directly regulated by the oncogene ZNF217 using chromatin immunoprecipitation (ChIP)-chip assays. J Biol Chem. 2007 Mar 30;282(13):9703-12. Epub 2007 Jan 26. PMID:17259635 doi:10.1074/jbc.M611752200
- ↑ Thillainadesan G, Isovic M, Loney E, Andrews J, Tini M, Torchia J. Genome analysis identifies the p15ink4b tumor suppressor as a direct target of the ZNF217/CoREST complex. Mol Cell Biol. 2008 Oct;28(19):6066-77. doi: 10.1128/MCB.00246-08. Epub 2008 Jul , 14. PMID:18625718 doi:10.1128/MCB.00246-08
- ↑ Quinlan KG, Nardini M, Verger A, Francescato P, Yaswen P, Corda D, Bolognesi M, Crossley M. Specific recognition of ZNF217 and other zinc finger proteins at a surface groove of C-terminal binding proteins. Mol Cell Biol. 2006 Nov;26(21):8159-72. Epub 2006 Aug 28. PMID:16940172 doi:10.1128/MCB.00680-06
- ↑ Vandevenne M, Jacques DA, Artuz C, Nguyen CD, Kwan AH, Segal DJ, Matthews JM, Crossley M, Guss JM, Mackay JP. New insights into DNA recognition by zinc fingers revealed by structural analysis of the oncoprotein ZNF217. J Biol Chem. 2013 Apr 12;288(15):10616-27. doi: 10.1074/jbc.M112.441451. Epub, 2013 Feb 22. PMID:23436653 doi:10.1074/jbc.M112.441451
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