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| | ==Solution structure of Miz-1 Zinc finger 10== | | ==Solution structure of Miz-1 Zinc finger 10== |
| - | <StructureSection load='7mc1' size='340' side='right'caption='[[7mc1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='7mc1' size='340' side='right'caption='[[7mc1]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7mc1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MC1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MC1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7mc1]] 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=7MC1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MC1 FirstGlance]. <br> |
| | </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> | | </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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ZBTB17, MIZ1, ZNF151, ZNF60 ([https://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=7mc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mc1 OCA], [https://pdbe.org/7mc1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mc1 RCSB], [https://www.ebi.ac.uk/pdbsum/7mc1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mc1 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=7mc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mc1 OCA], [https://pdbe.org/7mc1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mc1 RCSB], [https://www.ebi.ac.uk/pdbsum/7mc1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mc1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ZBT17_HUMAN ZBT17_HUMAN]] Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment (By similarity). Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation.<ref>PMID:9312026</ref> <ref>PMID:9308237</ref> <ref>PMID:19164764</ref>
| + | [https://www.uniprot.org/uniprot/ZBT17_HUMAN ZBT17_HUMAN] Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment (By similarity). Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation.<ref>PMID:9312026</ref> <ref>PMID:9308237</ref> <ref>PMID:19164764</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Boisvert, O]] | + | [[Category: Boisvert O]] |
| - | [[Category: Lavigne, P]] | + | [[Category: Lavigne P]] |
| - | [[Category: C2h2]]
| + | |
| - | [[Category: Dna binding]]
| + | |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| - | [[Category: Zinc finger]]
| + | |
| Structural highlights
Function
ZBT17_HUMAN Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment (By similarity). Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation.[1] [2] [3]
Publication Abstract from PubMed
Miz-1 (ZBTB17) is a poly-zinc finger BTB/POZ transcription factor with 12 consecutive C2H2 zinc fingers (ZFs) that binds transcriptional start sites (TSSs) to regulate the expression of genes involved in cell development and proliferation. As of now, it is not known which of the 12 consecutive ZFs are responsible for the recognition of the 24 base pair consensus sequence found at these TSSs. Evidence suggests ZFs 7-12 plays this role. We provide validation for this and describe the structural and dynamical characterization of unprecedented conformational exchange in the linker between ZFs 10 and 11. This conformational exchange uncouples ZFs 7-10 from 11 and 12 and promotes a scanning-recognition mechanism through which the two segments cooperate to bind two sub-sites at both ends of the consensus. We further show that this can result in the coiling of TSSs as part of Miz-1's mechanism of transcriptional transactivation.
Zinc Fingers 10 and 11 of Miz-1 undergo conformational exchange to achieve specific DNA binding.,Boisvert O, Letourneau D, Delattre P, Tremblay C, Jolibois E, Montagne M, Lavigne P Structure. 2022 Apr 7;30(4):623-636.e5. doi: 10.1016/j.str.2021.12.001. Epub 2021, Dec 27. PMID:34963061[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Peukert K, Staller P, Schneider A, Carmichael G, Hanel F, Eilers M. An alternative pathway for gene regulation by Myc. EMBO J. 1997 Sep 15;16(18):5672-86. PMID:9312026 doi:10.1093/emboj/16.18.5672
- ↑ Schneider A, Peukert K, Eilers M, Hanel F. Association of Myc with the zinc-finger protein Miz-1 defines a novel pathway for gene regulation by Myc. Curr Top Microbiol Immunol. 1997;224:137-46. PMID:9308237
- ↑ Basu S, Liu Q, Qiu Y, Dong F. Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1433-8. doi: 10.1073/pnas.0804863106., Epub 2009 Jan 22. PMID:19164764 doi:10.1073/pnas.0804863106
- ↑ Boisvert O, Letourneau D, Delattre P, Tremblay C, Jolibois E, Montagne M, Lavigne P. Zinc Fingers 10 and 11 of Miz-1 undergo conformational exchange to achieve specific DNA binding. Structure. 2022 Apr 7;30(4):623-636.e5. doi: 10.1016/j.str.2021.12.001. Epub 2021, Dec 27. PMID:34963061 doi:http://dx.doi.org/10.1016/j.str.2021.12.001
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