2vi6: Difference between revisions
New page: left|200px<br /><applet load="2vi6" size="350" color="white" frame="true" align="right" spinBox="true" caption="2vi6, resolution 2.60Å" /> '''CRYSTAL STRUCTURE OF... |
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== | ==Crystal Structure of the Nanog Homeodomain== | ||
The transcription factor Nanog is an upstream regulator in early mammalian | <StructureSection load='2vi6' size='340' side='right'caption='[[2vi6]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2vi6]] is a 8 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=2VI6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VI6 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]] 2.6Å</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=2vi6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vi6 OCA], [https://pdbe.org/2vi6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vi6 RCSB], [https://www.ebi.ac.uk/pdbsum/2vi6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vi6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NANOG_MOUSE NANOG_MOUSE] Transcription regulator involved in inner cell mass and embryonic stem (ES) cells proliferation and self-renewal (PubMed:25825768). Imposes pluripotency on ES cells and prevents their differentiation towards extraembryonic endoderm and trophectoderm lineages. Blocks bone morphogenetic protein-induced mesoderm differentiation of ES cells by physically interacting with SMAD1 and interfering with the recruitment of coactivators to the active SMAD transcriptional complexes. Acts as a transcriptional activator or repressor. Binds optimally to the DNA consensus sequence 5'-TAAT[GT][GT]-3' or 5'-[CG][GA][CG]C[GC]ATTAN[GC]-3'. Binds to the POU5F1/OCT4 promoter (By similarity). Able to autorepress its expression in differentiating (ES) cells: binds to its own promoter following interaction with ZNF281/ZFP281, leading to recruitment of the NuRD complex and subsequent repression of expression. When overexpressed, promotes cells to enter into S phase and proliferation.[UniProtKB:Q9H9S0]<ref>PMID:12787504</ref> <ref>PMID:12787505</ref> <ref>PMID:14728807</ref> <ref>PMID:15502159</ref> <ref>PMID:16518401</ref> <ref>PMID:16791199</ref> <ref>PMID:16801560</ref> <ref>PMID:21915945</ref> <ref>PMID:22988117</ref> <ref>PMID:25825768</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vi/2vi6_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vi6 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The transcription factor Nanog is an upstream regulator in early mammalian development and a key determinant of pluripotency in embryonic stem cells. Nanog binds to promoter elements of hundreds of target genes and regulates their expression by an as yet unknown mechanism. Here, we report the crystal structure of the murine Nanog homeodomain (HD) and analysis of its interaction with a DNA element derived from the Tcf3 promoter. Two Nanog amino acid pairs, unique among HD sequences, appear to affect the mechanism of nonspecific DNA recognition as well as maintain the integrity of the structural scaffold. To assess selective DNA recognition by Nanog, we performed electrophoretic mobility shift assays using a panel of modified DNA binding sites and found that Nanog HD preferentially binds the TAAT(G/T)(G/T) motif. A series of rational mutagenesis experiments probing the role of six variant residues of Nanog on its DNA binding function establish their role in affecting binding affinity but not binding specificity. Together, the structural and functional evidence establish Nanog as a distant member of a Q50-type HD despite having considerable variation at the sequence level. | |||
Crystal structure and DNA binding of the homeodomain of the stem cell transcription factor Nanog.,Jauch R, Ng CK, Saikatendu KS, Stevens RC, Kolatkar PR J Mol Biol. 2008 Feb 22;376(3):758-70. Epub 2007 Dec 4. PMID:18177668<ref>PMID:18177668</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2vi6" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Jauch R]] | |||
[[Category: Jauch | [[Category: Kolatkar PR]] | ||
[[Category: Kolatkar | [[Category: Ng CKL]] | ||
[[Category: Ng | [[Category: Saitakendu KS]] | ||
[[Category: Saitakendu | [[Category: Stevens RC]] | ||
[[Category: Stevens | |||
