2ka6: Difference between revisions
New page: '''Unreleased structure''' The entry 2ka6 is ON HOLD Authors: Wojciak, J.M., Martinez-Yamout, M.A., Dyson, H.J., Wright, P.E. Description: Structure of protein complex ''Page seeded b... |
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The | ==NMR structure of the CBP-TAZ2/STAT1-TAD complex== | ||
<StructureSection load='2ka6' size='340' side='right'caption='[[2ka6]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ka6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. The February 2010 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Enhanceosome'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2010_2 10.2210/rcsb_pdb/mom_2010_2]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KA6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KA6 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2ka6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ka6 OCA], [https://pdbe.org/2ka6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ka6 RCSB], [https://www.ebi.ac.uk/pdbsum/2ka6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ka6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CBP_MOUSE CBP_MOUSE] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300 (By similarity).<ref>PMID:10207073</ref> <ref>PMID:11701890</ref> <ref>PMID:15220471</ref> <ref>PMID:16287980</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/ka/2ka6_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=2ka6 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CBP/p300 transcriptional coactivators mediate gene expression by integrating cellular signals through interactions with multiple transcription factors. To elucidate the molecular and structural basis for CBP-dependent gene expression, we determined structures of the CBP TAZ1 and TAZ2 domains in complex with the transactivation domains (TADs) of signal transducer and activator of transcription 2 (STAT2) and STAT1, respectively. Despite the topological similarity of the TAZ1 and TAZ2 domains, subtle differences in helix packing and surface grooves constitute major determinants of target selectivity. Our results suggest that TAZ1 preferentially binds long TADs capable of contacting multiple surface grooves simultaneously, whereas smaller TADs that are restricted to a single contiguous binding surface form complexes with TAZ2. Complex formation for both STAT TADs involves coupled folding and binding, driven by intermolecular hydrophobic and electrostatic interactions. Phosphorylation of S727, required for maximal transcriptional activity of STAT1, does not enhance binding to any of the CBP domains. Because the different STAT TADs recognize different regions of CBP/p300, there is a potential for multivalent binding by STAT heterodimers that could enhance the recruitment of the coactivators to promoters. | |||
Structural basis for recruitment of CBP/p300 coactivators by STAT1 and STAT2 transactivation domains.,Wojciak JM, Martinez-Yamout MA, Dyson HJ, Wright PE EMBO J. 2009 Apr 8;28(7):948-58. Epub 2009 Feb 12. PMID:19214187<ref>PMID:19214187</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ka6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Enhanceosome]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: RCSB PDB Molecule of the Month]] | |||
[[Category: Dyson HJ]] | |||
[[Category: Martinez-Yamout MA]] | |||
[[Category: Wojciak JM]] | |||
[[Category: Wright PE]] | |||
Latest revision as of 12:46, 9 May 2024
NMR structure of the CBP-TAZ2/STAT1-TAD complexNMR structure of the CBP-TAZ2/STAT1-TAD complex
Structural highlights
FunctionCBP_MOUSE Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300 (By similarity).[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCBP/p300 transcriptional coactivators mediate gene expression by integrating cellular signals through interactions with multiple transcription factors. To elucidate the molecular and structural basis for CBP-dependent gene expression, we determined structures of the CBP TAZ1 and TAZ2 domains in complex with the transactivation domains (TADs) of signal transducer and activator of transcription 2 (STAT2) and STAT1, respectively. Despite the topological similarity of the TAZ1 and TAZ2 domains, subtle differences in helix packing and surface grooves constitute major determinants of target selectivity. Our results suggest that TAZ1 preferentially binds long TADs capable of contacting multiple surface grooves simultaneously, whereas smaller TADs that are restricted to a single contiguous binding surface form complexes with TAZ2. Complex formation for both STAT TADs involves coupled folding and binding, driven by intermolecular hydrophobic and electrostatic interactions. Phosphorylation of S727, required for maximal transcriptional activity of STAT1, does not enhance binding to any of the CBP domains. Because the different STAT TADs recognize different regions of CBP/p300, there is a potential for multivalent binding by STAT heterodimers that could enhance the recruitment of the coactivators to promoters. Structural basis for recruitment of CBP/p300 coactivators by STAT1 and STAT2 transactivation domains.,Wojciak JM, Martinez-Yamout MA, Dyson HJ, Wright PE EMBO J. 2009 Apr 8;28(7):948-58. Epub 2009 Feb 12. PMID:19214187[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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