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| | ==mouseZFP568-ZnF1-11 in complex with DNA== | | ==mouseZFP568-ZnF1-11 in complex with DNA== |
| - | <StructureSection load='5v3m' size='340' side='right' caption='[[5v3m]], [[Resolution|resolution]] 2.09Å' scene=''> | + | <StructureSection load='5v3m' size='340' side='right'caption='[[5v3m]], [[Resolution|resolution]] 2.09Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5v3m]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V3M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V3M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v3m]] 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=5V3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V3M FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.091Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5v3g|5v3g]], [[5v3j|5v3j]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5v3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v3m OCA], [http://pdbe.org/5v3m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v3m RCSB], [http://www.ebi.ac.uk/pdbsum/5v3m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v3m ProSAT]</span></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=5v3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v3m OCA], [https://pdbe.org/5v3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v3m RCSB], [https://www.ebi.ac.uk/pdbsum/5v3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v3m ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ZN568_MOUSE ZN568_MOUSE]] Has transcriptional repression activity, partially through the recruitment of the corepressor TRIM28 but has also repression activity independently of this interaction (PubMed:22110054, PubMed:27658112). Essential during embryonic development, where it acts as direct repressor of IGF2-P0, placental-specific transcript of IGF2, in early development and regulates convergent extension movements required for axis elongation and tissue morphogenesis in all germ layers (PubMed:18701545, PubMed:22110054, PubMed:28522536). Also important for normal morphogenesis of extraembryonic tissues including the yolk sac, extraembryonic mesoderm and placenta (PubMed:18701545, PubMed:21094155). May enhance proliferation or maintenance of neural stem cells (PubMed:23071813).<ref>PMID:18701545</ref> <ref>PMID:21094155</ref> <ref>PMID:22110054</ref> <ref>PMID:23071813</ref> <ref>PMID:27658112</ref> | + | [https://www.uniprot.org/uniprot/ZN568_MOUSE ZN568_MOUSE] Has transcriptional repression activity, partially through the recruitment of the corepressor TRIM28 but has also repression activity independently of this interaction (PubMed:22110054, PubMed:27658112). Essential during embryonic development, where it acts as direct repressor of IGF2-P0, placental-specific transcript of IGF2, in early development and regulates convergent extension movements required for axis elongation and tissue morphogenesis in all germ layers (PubMed:18701545, PubMed:22110054, PubMed:28522536). Also important for normal morphogenesis of extraembryonic tissues including the yolk sac, extraembryonic mesoderm and placenta (PubMed:18701545, PubMed:21094155). May enhance proliferation or maintenance of neural stem cells (PubMed:23071813).<ref>PMID:18701545</ref> <ref>PMID:21094155</ref> <ref>PMID:22110054</ref> <ref>PMID:23071813</ref> <ref>PMID:27658112</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 (Igf2-P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2-P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand. These interactions arise from a shortened minor groove caused by an AT-rich stretch, suggesting adaptability of ZF arrays to sequence variations. Despite conservation in mammals, mutations at Igf2 and ZFP568 reduce their binding affinity in chimpanzee and humans. Our studies provide important insights into the evolutionary and structural dynamics of ZF-DNA interactions that play a key role in mammalian development and evolution. |
| | + | |
| | + | DNA Conformation Induces Adaptable Binding by Tandem Zinc Finger Proteins.,Patel A, Yang P, Tinkham M, Pradhan M, Sun MA, Wang Y, Hoang D, Wolf G, Horton JR, Zhang X, Macfarlan T, Cheng X Cell. 2018 Mar 22;173(1):221-233.e12. doi: 10.1016/j.cell.2018.02.058. Epub 2018 , Mar 15. PMID:29551271<ref>PMID:29551271</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 5v3m" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cheng, X]] | + | [[Category: Large Structures]] |
| - | [[Category: Patel, A]] | + | [[Category: Mus musculus]] |
| - | [[Category: C2h2 type zinc finger]] | + | [[Category: Cheng X]] |
| - | [[Category: Dna binding]] | + | [[Category: Patel A]] |
| - | [[Category: Dna binding protein-dna complex]]
| + | |
| - | [[Category: Transferase-dna complex]]
| + | |
| Structural highlights
Function
ZN568_MOUSE Has transcriptional repression activity, partially through the recruitment of the corepressor TRIM28 but has also repression activity independently of this interaction (PubMed:22110054, PubMed:27658112). Essential during embryonic development, where it acts as direct repressor of IGF2-P0, placental-specific transcript of IGF2, in early development and regulates convergent extension movements required for axis elongation and tissue morphogenesis in all germ layers (PubMed:18701545, PubMed:22110054, PubMed:28522536). Also important for normal morphogenesis of extraembryonic tissues including the yolk sac, extraembryonic mesoderm and placenta (PubMed:18701545, PubMed:21094155). May enhance proliferation or maintenance of neural stem cells (PubMed:23071813).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 (Igf2-P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2-P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand. These interactions arise from a shortened minor groove caused by an AT-rich stretch, suggesting adaptability of ZF arrays to sequence variations. Despite conservation in mammals, mutations at Igf2 and ZFP568 reduce their binding affinity in chimpanzee and humans. Our studies provide important insights into the evolutionary and structural dynamics of ZF-DNA interactions that play a key role in mammalian development and evolution.
DNA Conformation Induces Adaptable Binding by Tandem Zinc Finger Proteins.,Patel A, Yang P, Tinkham M, Pradhan M, Sun MA, Wang Y, Hoang D, Wolf G, Horton JR, Zhang X, Macfarlan T, Cheng X Cell. 2018 Mar 22;173(1):221-233.e12. doi: 10.1016/j.cell.2018.02.058. Epub 2018 , Mar 15. PMID:29551271[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Garcia-Garcia MJ, Shibata M, Anderson KV. Chato, a KRAB zinc-finger protein, regulates convergent extension in the mouse embryo. Development. 2008 Sep;135(18):3053-62. doi: 10.1242/dev.022897. Epub 2008 Aug 13. PMID:18701545 doi:http://dx.doi.org/10.1242/dev.022897
- ↑ Shibata M, Garcia-Garcia MJ. The mouse KRAB zinc-finger protein CHATO is required in embryonic-derived tissues to control yolk sac and placenta morphogenesis. Dev Biol. 2011 Jan 15;349(2):331-41. doi: 10.1016/j.ydbio.2010.11.015. Epub 2010 , Nov 19. PMID:21094155 doi:http://dx.doi.org/10.1016/j.ydbio.2010.11.015
- ↑ Shibata M, Blauvelt KE, Liem KF Jr, Garcia-Garcia MJ. TRIM28 is required by the mouse KRAB domain protein ZFP568 to control convergent extension and morphogenesis of extra-embryonic tissues. Development. 2011 Dec;138(24):5333-43. doi: 10.1242/dev.072546. PMID:22110054 doi:http://dx.doi.org/10.1242/dev.072546
- ↑ Chien HC, Wang HY, Su YN, Lai KY, Lu LC, Chen PC, Tsai SF, Wu CI, Hsieh WS, Shen CK. Targeted disruption in mice of a neural stem cell-maintaining, KRAB-Zn finger-encoding gene that has rapidly evolved in the human lineage. PLoS One. 2012;7(10):e47481. doi: 10.1371/journal.pone.0047481. Epub 2012 Oct 10. PMID:23071813 doi:http://dx.doi.org/10.1371/journal.pone.0047481
- ↑ Murphy KE, Shylo NA, Alexander KA, Churchill AJ, Copperman C, Garcia-Garcia MJ. The Transcriptional Repressive Activity of KRAB Zinc Finger Proteins Does Not Correlate with Their Ability to Recruit TRIM28. PLoS One. 2016 Sep 22;11(9):e0163555. doi: 10.1371/journal.pone.0163555., eCollection 2016. PMID:27658112 doi:http://dx.doi.org/10.1371/journal.pone.0163555
- ↑ Patel A, Yang P, Tinkham M, Pradhan M, Sun MA, Wang Y, Hoang D, Wolf G, Horton JR, Zhang X, Macfarlan T, Cheng X. DNA Conformation Induces Adaptable Binding by Tandem Zinc Finger Proteins. Cell. 2018 Mar 22;173(1):221-233.e12. doi: 10.1016/j.cell.2018.02.058. Epub 2018 , Mar 15. PMID:29551271 doi:http://dx.doi.org/10.1016/j.cell.2018.02.058
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