View source for 8ek3


==Human PU.1 ETS-Domain (165-270) Q226E Mutant Bound to d(AATAAGCGGAATGGGG)==
<StructureSection load='8ek3' size='340' side='right'caption='[[8ek3]], [[Resolution|resolution]] 1.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ek3]] is a 3 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=8EK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EK3 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]] 1.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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=8ek3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ek3 OCA], [https://pdbe.org/8ek3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ek3 RCSB], [https://www.ebi.ac.uk/pdbsum/8ek3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ek3 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SPI1_HUMAN SPI1_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/SPI1_HUMAN SPI1_HUMAN] Pioneer transcription factor, which controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing other transcription factors to enter otherwise inaccessible genomic sites. Once in open chromatin, can directly control gene expression by binding genetic regulatory elements and can also more broadly influence transcription by recruiting transcription factors, such as interferon regulatory factors (IRFs), to otherwise inaccessible genomic regions (PubMed:23658224, PubMed:33951726). Transcriptionally activates genes important for myeloid and lymphoid lineages, such as CSF1R (By similarity). Transcriptional activation from certain promoters, possibly containing low affinity binding sites, is achieved cooperatively with other transcription factors. FCER1A transactivation is achieved in cooperation with GATA1 (By similarity). May be particularly important for the pro- to pre-B cell transition (PubMed:33951726). Binds (via the ETS domain) onto the purine-rich DNA core sequence 5'-GAGGAA-3', also known as the PU-box (PubMed:33951726). In vitro can bind RNA and interfere with pre-mRNA splicing (By similarity).[UniProtKB:P17433][UniProtKB:Q6BDS1]<ref>PMID:23658224</ref> <ref>PMID:33951726</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The master transcriptional regulator PU.1/Spi-1 engages DNA sites with affinities spanning multiple orders of magnitude. To elucidate this remarkable plasticity, we have characterized 22 high-resolution co-crystallographic PU.1/DNA complexes across the addressable affinity range in myeloid gene transactivation. Over a purine-rich core (such as 5'-GGAA-3') flanked by variable sequences, affinity is negotiated by direct readout on the 5' flank via a critical glutamine (Q226) sidechain and by indirect readout on the 3' flank by sequence-dependent helical flexibility. Direct readout by Q226 dynamically specifies PU.1's characteristic preference for purines and explains the pathogenic mutation Q226E in Waldenstrom macroglobulinemia. The structures also reveal how disruption of Q226 mediates strand-specific inhibition by DNA methylation and the recognition of non-canonical sites, including the authentic binding sequence at the CD11b promoter. A re-synthesis of phylogenetic and structural data on the ETS family, considering the centrality of Q226 in PU.1, unifies the model of DNA selection by ETS proteins.

DNA selection by the master transcription factor PU.1.,Terrell JR, Taylor SJ, Schneider AL, Lu Y, Vernon TN, Xhani S, Gumpper RH, Luo M, Wilson WD, Steidl U, Poon GMK Cell Rep. 2023 Jun 22;42(7):112671. doi: 10.1016/j.celrep.2023.112671. PMID:37352101<ref>PMID:37352101</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ek3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Poon GMK]]
[[Category: Terrell JR]]