View source for 6qhd


==Lysine acetylated and tyrosine phosphorylated STAT3 in a complex with DNA==
<StructureSection load='6qhd' size='340' side='right'caption='[[6qhd]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qhd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Murine_adenovirus_1 Murine adenovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QHD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QHD 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]] 2.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=6qhd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qhd OCA], [https://pdbe.org/6qhd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qhd RCSB], [https://www.ebi.ac.uk/pdbsum/6qhd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qhd ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/STAT3_HUMAN STAT3_HUMAN] Chronic lymphoproliferative disorder of natural killer cells;Autosomal dominant hyper-IgE syndrome;STAT3-related early-onset multisystem autoimmune disease;T-cell large granular lymphocyte leukemia;Permanent neonatal diabetes mellitus. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/STAT3_HUMAN STAT3_HUMAN] Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, PubMed:15194700, PubMed:17344214, PubMed:18242580, PubMed:23084476). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:17344214). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes (PubMed:12359225). Activated by IL31 through IL31RA (PubMed:15194700). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): deacetylation and oxidation of lysine residues by LOXL3, leads to disrupt STAT3 dimerization and inhibit its transcription activity (PubMed:28065600). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity).[UniProtKB:P42227]<ref>PMID:10688651</ref> <ref>PMID:12359225</ref> <ref>PMID:12873986</ref> <ref>PMID:15194700</ref> <ref>PMID:17344214</ref> <ref>PMID:18242580</ref> <ref>PMID:23084476</ref> <ref>PMID:28065600</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The signal transducer and activator of transcription 3 (STAT3) protein is activated by phosphorylation of a specific tyrosine residue (Tyr705) in response to various extracellular signals. STAT3 activity was also found to be regulated by acetylation of Lys685. However, the molecular mechanism by which Lys685 acetylation affects the transcriptional activity of STAT3 remains elusive. By genetically encoding the co-translational incorporation of acetyl-lysine into position Lys685 and co-expression of STAT3 with the Elk receptor tyrosine kinase, we were able to characterize site-specifically acetylated, and simultaneously acetylated and phosphorylated STAT3. We measured the effect of acetylation on the crystal structure, and DNA binding affinity and specificity of Tyr705-phosphorylated and non-phosphorylated STAT3. In addition, we monitored the deacetylation of acetylated Lys685 by reconstituting the mammalian enzymatic deacetylation reaction in live bacteria. Surprisingly, we found that acetylation, per se, had no effect on the crystal structure, and DNA binding affinity or specificity of STAT3, implying that the previously observed acetylation-dependent transcriptional activity of STAT3 involves an additional cellular component. In addition, we discovered that Tyr705-phosphorylation protects Lys685 from deacetylation in bacteria, providing a new possible explanation for the observed correlation between STAT3 activity and Lys685 acetylation.

Unexpected implications of STAT3 acetylation revealed by genetic encoding of acetyl-lysine.,Belo Y, Mielko Z, Nudelman H, Afek A, Ben-David O, Shahar A, Zarivach R, Gordan R, Arbely E Biochim Biophys Acta Gen Subj. 2019 Jun 3;1863(9):1343-1350. doi:, 10.1016/j.bbagen.2019.05.019. PMID:31170499<ref>PMID:31170499</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qhd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Murine adenovirus 1]]
[[Category: Arbely E]]
[[Category: Belo Y]]
[[Category: Shahar A]]
[[Category: Zarivach R]]