2lxt: Difference between revisions
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The | ==Allosteric communication in the KIX domain proceeds through dynamic re-packing of the hydrophobic core== | ||
<StructureSection load='2lxt' size='340' side='right'caption='[[2lxt]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2lxt]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LXT FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=2lxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lxt OCA], [https://pdbe.org/2lxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lxt RCSB], [https://www.ebi.ac.uk/pdbsum/2lxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lxt ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Note=Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with KAT6A; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with KAT6B. KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription. Defects in CREBBP are a cause of Rubinstein-Taybi syndrome type 1 (RSTS1) [MIM:[https://omim.org/entry/180849 180849]. RSTS1 is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.<ref>PMID:11331617</ref> <ref>PMID:12114483</ref> <ref>PMID:12566391</ref> <ref>PMID:15706485</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] 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.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The KIX domain of the transcriptional coactivator CREB binding protein (CBP) co-operatively mediates interactions between transcription factors. Binding of the transcription factor mixed-lineage leukemia (MLL) induces the formation of a low-populated conformer of KIX that resembles the conformation of the KIX domain in the presence of a second transcription factor molecule. NMR spin relaxation studies have previously shown that allosteric coupling proceeds through a network of hydrophobic core residues that bridge the two binding sites. Here we describe high-resolution NMR solution structures of the binary complex of KIX with MLL and the ternary complex of KIX formed with MLL and phosphorylated kinase inducible domain of CREB (pKID) as a second ligand. We show that binding of pKID to the binary complex of KIX with MLL is accompanied by a defined repacking of the allosteric network in the hydrophobic core of the protein. Rotamer populations derived from methyl group 13C chemical shifts reveal a dynamic contribution to the repacking process that is not captured by the structural coordinates and exemplify the dynamic nature of allosteric communication in the KIX domain. | |||
Allosteric Communication in the KIX Domain Proceeds through Dynamic Repacking of the Hydrophobic Core.,Bruschweiler S, Konrat R, Tollinger M ACS Chem Biol. 2013 May 20. PMID:23651431<ref>PMID:23651431</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2lxt" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bruschweiler S]] | |||
[[Category: Konrat R]] | |||
[[Category: Schanda P]] | |||
[[Category: Tollinger M]] | |||
