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| | ==NMR structure of the basic helix-loop-helix region of the transcriptional repressor HES-1== | | ==NMR structure of the basic helix-loop-helix region of the transcriptional repressor HES-1== |
| - | <StructureSection load='2mh3' size='340' side='right' caption='[[2mh3]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mh3' size='340' side='right'caption='[[2mh3]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mh3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MH3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MH3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mh3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MH3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MH3 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HES1, BHLHB39, HL, HRY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HES1, BHLHB39, HL, HRY ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mh3 OCA], [http://pdbe.org/2mh3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mh3 RCSB], [http://www.ebi.ac.uk/pdbsum/2mh3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mh3 ProSAT]</span></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=2mh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mh3 OCA], [https://pdbe.org/2mh3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mh3 RCSB], [https://www.ebi.ac.uk/pdbsum/2mh3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mh3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HES1_HUMAN HES1_HUMAN]] Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity (By similarity). May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage.<ref>PMID:18550849</ref> | + | [[https://www.uniprot.org/uniprot/HES1_HUMAN HES1_HUMAN]] Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity (By similarity). May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage.<ref>PMID:18550849</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Boelens, R]] | | [[Category: Boelens, R]] |
| | [[Category: Coglievina, M]] | | [[Category: Coglievina, M]] |
| Structural highlights
Function
[HES1_HUMAN] Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity (By similarity). May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage.[1]
Publication Abstract from PubMed
HES-1, one of the main downstream effectors in Notch signaling, is a transcriptional repressor of the basic helix-loop-helix (bHLH) family. Using NMR methods, we have determined the structure and dynamics of a recombinant protein, H1H, which includes an N-terminal segment, b1, containing functionally important phosphorylation sites, the basic region b2, required for binding to DNA, and the helix-loop-helix domain (HLH). We show that a proline residue in the sequence divides the protein in two parts, a flexible and disordered N-terminal region including b1 and a structured, mainly helical region comprising b2 and the HLH domain. Binding of H1H to a dsDNA oligonucleotide was monitored through the chemical shift perturbation of backbone amide resonances, and showed that the interaction surface involves not only the b2 segment, but also several residues in the b1 and HLH regions. (c) Proteins 2014;. (c) 2014 Wiley Periodicals, Inc.
The basic-helix-loop-helix region of the transcriptional repressor HES-1 is preorganized to bind DNA.,Popovic M, Wienk H, Coglievina M, Boelens R, Pongor S, Pintar A Proteins. 2014 Jan 8. doi: 10.1002/prot.24507. PMID:24403087[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tremblay CS, Huang FF, Habi O, Huard CC, Godin C, Levesque G, Carreau M. HES1 is a novel interactor of the Fanconi anemia core complex. Blood. 2008 Sep 1;112(5):2062-70. doi: 10.1182/blood-2008-04-152710. Epub 2008, Jun 11. PMID:18550849 doi:http://dx.doi.org/10.1182/blood-2008-04-152710
- ↑ Popovic M, Wienk H, Coglievina M, Boelens R, Pongor S, Pintar A. The basic-helix-loop-helix region of the transcriptional repressor HES-1 is preorganized to bind DNA. Proteins. 2014 Jan 8. doi: 10.1002/prot.24507. PMID:24403087 doi:http://dx.doi.org/10.1002/prot.24507
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