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8h9h
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of ZBTB7A in complex with GACCC-containing sequence== | |
| + | <StructureSection load='8h9h' size='340' side='right'caption='[[8h9h]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8h9h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8H9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8H9H FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=8h9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8h9h OCA], [https://pdbe.org/8h9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8h9h RCSB], [https://www.ebi.ac.uk/pdbsum/8h9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8h9h ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ZBT7A_HUMAN ZBT7A_HUMAN] Plays a key role in the instruction of early lymphoid progenitors to develop into B lineage by repressing T-cell instructive Notch signals (By similarity). Specifically represses the transcription of the CDKN2A gene. Efficiently abrogates E2F1-dependent CDKN2A transactivation/de-repression. Binds to the consensus sequence 5'-[GA][CA]GACCCCCCCCC-3' (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | ZBTB7A, a transcription factor containing a tandem array of four Cys2-His2 zinc fingers (ZFs), is vital for multiple physiological events through directional binding to different genomic loci. Our previously determined crystal structure of ZBTB7A in complex with a GCCCCTTCCCC sequence revealed that all four ZFs (ZF1-4) are involved in binding to gamma-globin -200 gene element to repress fetal haemoglobin expression. Recently, it has been reported that ZBTB7A drives primed-to-naive transition (PNT) of pluripotent stem cells through binding to a 12-bp consensus sequence ([AAGGACCCAGAT], referred to as PNT-associated sequence). Here, we report a crystal structure of ZBTB7A ZF1-3 in complex with the PNT-associated sequence. The structure shows that ZF1 and ZF2 primarily contribute to recognizing the GACCC core sequence mimicking the half part (GCCCC) of gamma-globin -200 gene element via specific hydrogen bonding and van der Waals contacts. The mutations of key residues in ZF1-2 remarkably reduce their binding affinities for the PNT-associated sequence in vitro and cannot restore epiblast stem cells to the naive pluripotent state in vivo. Collectively, our studies demonstrate that ZBTB7A mainly employs its ZF1-2 to recognize the PNT-associated sequence but recognizes gamma-globin -200 gene element via ZF1-4, providing insights into the molecular mechanism for the diversity of ZBTB7A's genomic localization. | ||
| - | + | ZBTB7A regulates primed-to-naive transition of pluripotent stem cells via recognition of the PNT-associated sequence by zinc fingers 1-2 and recognition of gamma-globin -200 gene element by zinc fingers 1-4.,Yang Y, Xiao L, Xue Y, Idris MO, Liu J, Pei D, Shi Y, Liao B, Li F FEBS J. 2023 Apr 4. doi: 10.1111/febs.16789. PMID:37013936<ref>PMID:37013936</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8h9h" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Yang Y]] | ||
Current revision
Crystal structure of ZBTB7A in complex with GACCC-containing sequence
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