1b72: Difference between revisions
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< | ==PBX1, HOMEOBOX PROTEIN HOX-B1/DNA TERNARY COMPLEX== | ||
<StructureSection load='1b72' size='340' side='right'caption='[[1b72]], [[Resolution|resolution]] 2.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1b72]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B72 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B72 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35Å</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=1b72 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b72 OCA], [https://pdbe.org/1b72 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b72 RCSB], [https://www.ebi.ac.uk/pdbsum/1b72 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b72 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/PBX1_HUMAN PBX1_HUMAN] Note=A chromosomal aberration involving PBX1 is a cause of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with TCF3. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PBX1_HUMAN PBX1_HUMAN] Binds the sequence 5'-ATCAATCAA-3'. Acts as a transcriptional activator of PF4 in complex with MEIS1. Converted into a potent transcriptional activator by the (1;19) translocation. May have a role in steroidogenesis and, subsequently, sexual development and differentiation. Isoform PBX1b as part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Probably in complex with MEIS2, is involved in transcriptional regulation by KLF4.<ref>PMID:12609849</ref> <ref>PMID:21746878</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/b7/1b72_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=1b72 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Hox homeodomain proteins are developmental regulators that determine body plan in a variety of organisms. A majority of the vertebrate Hox proteins bind DNA as heterodimers with the Pbx1 homeodomain protein. We report here the 2.35 A structure of a ternary complex containing a human HoxB1-Pbx1 heterodimer bound to DNA. Heterodimer contacts are mediated by the hexapeptide of HoxB1, which binds in a pocket in the Pbx1 protein formed in part by a three-amino acid insertion in the Pbx1 homeodomain. The Pbx1 DNA-binding domain is larger than the canonical homeodomain, containing an additional alpha helix that appears to contribute to binding of the HoxB1 hexapeptide and to stable binding of Pbx1 to DNA. The structure suggests a model for modulation of Hox DNA binding activity by Pbx1 and related proteins. | Hox homeodomain proteins are developmental regulators that determine body plan in a variety of organisms. A majority of the vertebrate Hox proteins bind DNA as heterodimers with the Pbx1 homeodomain protein. We report here the 2.35 A structure of a ternary complex containing a human HoxB1-Pbx1 heterodimer bound to DNA. Heterodimer contacts are mediated by the hexapeptide of HoxB1, which binds in a pocket in the Pbx1 protein formed in part by a three-amino acid insertion in the Pbx1 homeodomain. The Pbx1 DNA-binding domain is larger than the canonical homeodomain, containing an additional alpha helix that appears to contribute to binding of the HoxB1 hexapeptide and to stable binding of Pbx1 to DNA. The structure suggests a model for modulation of Hox DNA binding activity by Pbx1 and related proteins. | ||
Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation.,Piper DE, Batchelor AH, Chang CP, Cleary ML, Wolberger C Cell. 1999 Feb 19;96(4):587-97. PMID:10052460<ref>PMID:10052460</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1b72" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Hox protein|Hox protein]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Batchelor | [[Category: Batchelor AH]] | ||
[[Category: Chang | [[Category: Chang C-P]] | ||
[[Category: Cleary | [[Category: Cleary ML]] | ||
[[Category: Piper | [[Category: Piper DE]] | ||
[[Category: Wolberger | [[Category: Wolberger C]] | ||
Latest revision as of 02:20, 28 December 2023
PBX1, HOMEOBOX PROTEIN HOX-B1/DNA TERNARY COMPLEXPBX1, HOMEOBOX PROTEIN HOX-B1/DNA TERNARY COMPLEX
Structural highlights
DiseasePBX1_HUMAN Note=A chromosomal aberration involving PBX1 is a cause of pre-B-cell acute lymphoblastic leukemia (B-ALL). Translocation t(1;19)(q23;p13.3) with TCF3. TCF3-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family. FunctionPBX1_HUMAN Binds the sequence 5'-ATCAATCAA-3'. Acts as a transcriptional activator of PF4 in complex with MEIS1. Converted into a potent transcriptional activator by the (1;19) translocation. May have a role in steroidogenesis and, subsequently, sexual development and differentiation. Isoform PBX1b as part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Probably in complex with MEIS2, is involved in transcriptional regulation by KLF4.[1] [2] 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 PubMedHox homeodomain proteins are developmental regulators that determine body plan in a variety of organisms. A majority of the vertebrate Hox proteins bind DNA as heterodimers with the Pbx1 homeodomain protein. We report here the 2.35 A structure of a ternary complex containing a human HoxB1-Pbx1 heterodimer bound to DNA. Heterodimer contacts are mediated by the hexapeptide of HoxB1, which binds in a pocket in the Pbx1 protein formed in part by a three-amino acid insertion in the Pbx1 homeodomain. The Pbx1 DNA-binding domain is larger than the canonical homeodomain, containing an additional alpha helix that appears to contribute to binding of the HoxB1 hexapeptide and to stable binding of Pbx1 to DNA. The structure suggests a model for modulation of Hox DNA binding activity by Pbx1 and related proteins. Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation.,Piper DE, Batchelor AH, Chang CP, Cleary ML, Wolberger C Cell. 1999 Feb 19;96(4):587-97. PMID:10052460[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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