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New page: left|200px<br /> <applet load="2agh" size="450" color="white" frame="true" align="right" spinBox="true" caption="2agh" /> '''Structural basis for cooperative transcript...
 
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[[Image:2agh.gif|left|200px]]<br />
<applet load="2agh" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2agh" />
'''Structural basis for cooperative transcription factor binding to the CBP coactivator'''<br />


==Overview==
==Structural basis for cooperative transcription factor binding to the CBP coactivator==
Regulation of transcription requires interactions between transcriptional, activators and transcriptional co-activator CREB binding protein (CBP)., The KIX domain of CBP can bind simultaneously to two different proteins, providing an additional mechanism for transcriptional regulation. Here we, describe the solution structure of the ternary complex formed by, cooperative binding of activation domains from the c-Myb and mixed lineage, leukemia (MLL) transcription factors to the KIX domain. The MLL and c-Myb, domains form helices that bind to two distinct hydrophobic grooves on, opposite faces of KIX. Compared to the binary KIX:c-Myb complex, significant changes are observed in the structure of KIX at the MLL, binding interface in the ternary complex. Two regions of KIX that are, disordered in the binary complex become structured in the ternary complex:, a flexible loop forms intimate contacts with bound MLL, and the C-terminal, helix is extended and stabilized by MLL binding. This structural change, results in the formation of additional electrostatic/polar interactions, between KIX and the bound c-Myb, providing a structural basis for the, cooperativity observed for the ternary complex.
<StructureSection load='2agh' size='340' side='right'caption='[[2agh]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2agh]] is a 3 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 experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AGH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AGH 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=2agh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2agh OCA], [https://pdbe.org/2agh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2agh RCSB], [https://www.ebi.ac.uk/pdbsum/2agh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2agh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MYB_MOUSE MYB_MOUSE] Transcriptional activator; DNA-binding protein that specifically recognize the sequence 5'-YAAC[GT]G-3'. Plays an important role in the control of proliferation and differentiation of hematopoietic progenitor cells.
== 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/ag/2agh_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=2agh ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known diseases associated with this structure: Leukemia, myeloid/lymphoid or mixed-lineage OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=159555 159555]]
*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]]
 
*[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]]
==About this Structure==
__TOC__
2AGH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2AGH OCA].
</StructureSection>
 
==Reference==
Structural basis for cooperative transcription factor binding to the CBP coactivator., De Guzman RN, Goto NK, Dyson HJ, Wright PE, J Mol Biol. 2006 Feb 3;355(5):1005-13. Epub 2005 Oct 5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16253272 16253272]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Protein complex]]
[[Category: De Guzman RN]]
[[Category: Dyson, H.J.]]
[[Category: Dyson HJ]]
[[Category: Goto, N.K.]]
[[Category: Goto NK]]
[[Category: Guzman, R.N.De.]]
[[Category: Wright PE]]
[[Category: Wright, P.E.]]
[[Category: transcription]]
 
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