1s7e: Difference between revisions

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New page: left|200px<br /><applet load="1s7e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s7e" /> '''Solution structure of HNF-6'''<br /> ==Over...
 
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[[Image:1s7e.gif|left|200px]]<br /><applet load="1s7e" size="450" color="white" frame="true" align="right" spinBox="true"
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'''Solution structure of HNF-6'''<br />


==Overview==
==Solution structure of HNF-6==
Hepatocyte nuclear factor 6 (HNF-6) belongs to the family of One Cut, transcription factors (also known as OC-1) and is essential for the, development of the mouse pancreas, gall bladder, and the interhepatic bile, ducts. HNF-6 binds to DNA as a monomer utilizing a single cut domain and a, divergent homeodomain motif located at its C terminus. Here, we have used, NMR methods to determine the solution structures of the 162 amino acid, residue DNA-binding domain of the HNF-6alpha protein. The resulting, overall structure of HNF-6alpha has two different distinct domains: the, Cut domain and the Homeodomain connected by a long flexible linker. Our, NMR structure shows that the Cut domain folds into a topology homologous, to the POU DNA-binding domain, even though the sequences of these two, protein families do not show homology. The DNA contact sequence of the, HNF-6alpha was mapped with chemical shift perturbation methods. Our data, also show that a proposed CREB-binding protein histone acetyltransferase, protein-recruiting sequence, LSDLL, forms a helix and is involved in the, hydrophobic core of the Cut domain. The structure implies that this, sequence has to undergo structural changes when it interacts with, CREB-binding protein.
<StructureSection load='1s7e' size='340' side='right'caption='[[1s7e]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1s7e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S7E FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1s7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s7e OCA], [https://pdbe.org/1s7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s7e RCSB], [https://www.ebi.ac.uk/pdbsum/1s7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s7e ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HNF6_MOUSE HNF6_MOUSE] Transcriptional activator. Binds the consensus sequence 5'-DHWATTGAYTWWD-3' on a variety of gene promoters such as those of HNF3B and TTR. Important for liver genes transcription. Stimulates the expression of Onecut3 in the developing endoderm.<ref>PMID:15381696</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/s7/1s7e_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1s7e ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hepatocyte nuclear factor 6 (HNF-6) belongs to the family of One Cut transcription factors (also known as OC-1) and is essential for the development of the mouse pancreas, gall bladder, and the interhepatic bile ducts. HNF-6 binds to DNA as a monomer utilizing a single cut domain and a divergent homeodomain motif located at its C terminus. Here, we have used NMR methods to determine the solution structures of the 162 amino acid residue DNA-binding domain of the HNF-6alpha protein. The resulting overall structure of HNF-6alpha has two different distinct domains: the Cut domain and the Homeodomain connected by a long flexible linker. Our NMR structure shows that the Cut domain folds into a topology homologous to the POU DNA-binding domain, even though the sequences of these two protein families do not show homology. The DNA contact sequence of the HNF-6alpha was mapped with chemical shift perturbation methods. Our data also show that a proposed CREB-binding protein histone acetyltransferase protein-recruiting sequence, LSDLL, forms a helix and is involved in the hydrophobic core of the Cut domain. The structure implies that this sequence has to undergo structural changes when it interacts with CREB-binding protein.


==About this Structure==
Structure of the hepatocyte nuclear factor 6alpha and its interaction with DNA.,Sheng W, Yan H, Rausa FM 3rd, Costa RH, Liao X J Biol Chem. 2004 Aug 6;279(32):33928-36. Epub 2004 May 28. PMID:15169783<ref>PMID:15169783</ref>
1S7E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1S7E OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structure of the hepatocyte nuclear factor 6alpha and its interaction with DNA., Sheng W, Yan H, Rausa FM 3rd, Costa RH, Liao X, J Biol Chem. 2004 Aug 6;279(32):33928-36. Epub 2004 May 28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15169783 15169783]
</div>
<div class="pdbe-citations 1s7e" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Liao X]]
[[Category: Liao, X.]]
[[Category: Sheng W]]
[[Category: Sheng, W.]]
[[Category: dna-binding]]
[[Category: homeobox]]
[[Category: nuclear protein]]
[[Category: transcription regulation]]
 
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Solution structure of HNF-6

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