2mh0
From Proteopedia
(Difference between revisions)
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<StructureSection load='2mh0' size='340' side='right'caption='[[2mh0]]' scene=''> | <StructureSection load='2mh0' size='340' side='right'caption='[[2mh0]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full | + | <table><tr><td colspan='2'>[[2mh0]] is a 2 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=2MH0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MH0 FirstGlance]. <br> |
| - | </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=2mh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mh0 OCA], [https://pdbe.org/2mh0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mh0 RCSB], [https://www.ebi.ac.uk/pdbsum/2mh0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mh0 ProSAT]</span></td></tr> | + | </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=2mh0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mh0 OCA], [https://pdbe.org/2mh0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mh0 RCSB], [https://www.ebi.ac.uk/pdbsum/2mh0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mh0 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/TFE2_HUMAN TFE2_HUMAN] Precursor B-cell acute lymphoblastic leukemia. Chromosomal aberrations involving TCF3 are cause of forms of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with PBX1. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family. Translocation t(17;19)(q22;p13.3) with HLF. Inversion inv(19)(p13;q13) with TFPT. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TFE2_HUMAN TFE2_HUMAN] Transcriptional regulator. Involved in the initiation of neuronal differentiation. Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation. Dimers bind DNA on E-box motifs: 5'-CANNTG-3'. Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer. Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The E-protein transcription factors guide immune cell differentiation, with E12 and E47 (hereafter called E2A) being essential for B-cell specification and maturation. E2A and the oncogenic chimera E2A-PBX1 contain three transactivation domains (ADs), with AD1 and AD2 having redundant, independent, and cooperative functions in a cell-dependent manner. AD1 and AD2 both mediate their functions by binding to the KIX domain of the histone acetyltransferase paralogues CREB-binding protein (CBP) and E1A-binding protein P300 (p300). This interaction is necessary for B-cell maturation and oncogenesis by E2A-PBX1 and occurs through conserved PhiXXPhiPhi motifs (with Phi denoting a hydrophobic amino acid) in AD1 and AD2. However, disruption of this interaction via mutation of the KIX domain in CBP/p300 does not completely abrogate binding of E2A and E2A-PBX1. Here, we determined that E2A-AD1 and E2A-AD2 also interact with the TAZ2 domain of CBP/p300. Characterization of the TAZ2:E2A-AD1(1-37) complex indicated that E2A-AD1 adopts an alpha-helical structure and uses its PhiXXPhiPhi motif to bind TAZ2. Whereas this region overlapped with the KIX recognition region, key KIX-interacting E2A-AD1 residues were exposed, suggesting that E2A-AD1 could simultaneously bind both the KIX and TAZ2 domains. However, we did not detect a ternary complex involving E2A-AD1, KIX, and TAZ2 and found that E2A containing both intact AD1 and AD2 is required to bind to CBP/p300. Our findings highlight the structural plasticity and promiscuity of E2A-AD1 and suggest that E2A binds both the TAZ2 and KIX domains of CBP/p300 through AD1 and AD2. | ||
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| + | Structural insights into TAZ2 domain-mediated CBP/p300 recruitment by transactivation domain 1 of the lymphopoietic transcription factor E2A.,Lochhead MR, Brown AD, Kirlin AC, Chitayat S, Munro K, Findlay JE, Baillie GS, LeBrun DP, Langelaan DN, Smith SP J Biol Chem. 2020 Mar 27;295(13):4303-4315. doi: 10.1074/jbc.RA119.011078. Epub , 2020 Feb 25. PMID:32098872<ref>PMID:32098872</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2mh0" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] | *[[Histone acetyltransferase 3D structures|Histone acetyltransferase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chitayat S]] | [[Category: Chitayat S]] | ||
[[Category: Langelaan DN]] | [[Category: Langelaan DN]] | ||
[[Category: Smith SP]] | [[Category: Smith SP]] | ||
Current revision
Solution NMR structure of the p300 Taz2:ETAD1 complex
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