1p4q

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[[Image:1p4q.png|left|200px]]
 
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{{STRUCTURE_1p4q| PDB=1p4q | SCENE= }}
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==Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain==
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<StructureSection load='1p4q' size='340' side='right'caption='[[1p4q]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1p4q]] 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=1P4Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P4Q FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 17 models</td></tr>
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<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>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p4q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p4q OCA], [https://pdbe.org/1p4q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p4q RCSB], [https://www.ebi.ac.uk/pdbsum/1p4q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p4q ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CITE2_HUMAN CITE2_HUMAN] Defects in CITED2 are a cause of ventricular septal defect type 2 (VSD2) [MIM:[https://omim.org/entry/614431 614431]. VSD2 is a common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death.<ref>PMID:16287139</ref> Defects in CITED2 are a cause of atrial septal defect type 8 (ASD8) [MIM:[https://omim.org/entry/614433 614433]. ASD8 is a congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria.<ref>PMID:16287139</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/CITE2_HUMAN CITE2_HUMAN] Transcriptional coactivator of the p300/CBP-mediated trancription complex. Acts as a bridge, linking TFAP2 transcription factors and the p300/CBP transcriptional coactivator complex in order to stimulate TFAP2-mediated transcriptional activation. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Stimulates the peroxisome proliferator-activated receptors PPARA transcriptional activity. Enhances estrogen-dependent transactivation mediated by estrogen receptors. Acts also as a transcriptional corepressor; interferes with the binding of the transcription factors HIF1A or STAT2 and the p300/CBP transcriptional coactivator complex. Participates in sex determination and early gonad development by stimulating transcription activation of SRY. Plays a role in controlling left-right patterning during embryogenesis; potentiates transcriptional activation of NODAL-mediated gene transcription in the left lateral plate mesoderm (LPM). Plays an essential role in differentiation of the adrenal cortex from the adrenogonadal primordium (AGP); stimulates WT1-mediated transcription activation thereby up-regulating the nuclear hormone receptor NR5A1 promoter activity. Associates with chromatin to the PITX2 P1 promoter region.<ref>PMID:11581164</ref> <ref>PMID:12586840</ref> <ref>PMID:15051727</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p4/1p4q_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1p4q ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Expression of hypoxia-responsive genes is mediated by the heterodimeric transcription factor hypoxia-inducible factor-1 (HIF-1) in complex with the p300/CREB-binding protein (p300/CBP) transcriptional coactivator. The protein CITED2, which binds p300/CBP, is thought to be a negative regulator of HIF-1 transactivation. We show that the CITED2 transactivation domain (TAD) disrupts a complex of the HIF-1alpha C-terminal TAD (C-TAD) and the cysteine-histidine-rich 1 (CH1) domain of p300/CBP by binding CH1 with high affinity. The high-resolution solution structure of the CITED2 TAD-p300 CH1 complex shows that the CITED2 TAD, like the HIF-1alpha C-TAD, folds on a helical, Zn2+-containing CH1 scaffold. The CITED2 TAD binds a different, more extensive surface of CH1 than does the HIF-1alpha C-TAD. However, a conserved 'LPXL' sequence motif in CITED2 and HIF-1alpha interacts with an overlapping binding site on CH1. Mutation of the LPEL sequence in full-length CITED2 abolishes p300 binding in vivo. These findings reveal that CITED2 regulates HIF-1 by competing for a hot spot on the p300 CH1 domain.
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===Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain===
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Structural basis for negative regulation of hypoxia-inducible factor-1alpha by CITED2.,Freedman SJ, Sun ZY, Kung AL, France DS, Wagner G, Eck MJ Nat Struct Biol. 2003 Jul;10(7):504-12. PMID:12778114<ref>PMID:12778114</ref>
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{{ABSTRACT_PUBMED_12778114}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 1p4q" style="background-color:#fffaf0;"></div>
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[[1p4q]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P4Q OCA].
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:012778114</ref><references group="xtra"/>
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</StructureSection>
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[[Category: Histone acetyltransferase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Eck, M J.]]
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[[Category: Large Structures]]
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[[Category: France, D S.]]
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[[Category: Eck MJ]]
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[[Category: Freedman, S J.]]
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[[Category: France DS]]
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[[Category: Kung, A L.]]
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[[Category: Freedman SJ]]
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[[Category: Sun, Z-Y J.]]
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[[Category: Kung AL]]
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[[Category: Wagner, G.]]
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[[Category: Sun Z-YJ]]
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[[Category: Helix]]
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[[Category: Wagner G]]
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[[Category: Protein-protein complex]]
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[[Category: Transcription-transferase complex]]
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Current revision

Solution structure of the CITED2 transactivation domain in complex with the p300 CH1 domain

PDB ID 1p4q

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