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| | ==Crystal structure of the complex of human chromobox homolog 2 (CBX2) and H3K27 peptide== | | ==Crystal structure of the complex of human chromobox homolog 2 (CBX2) and H3K27 peptide== |
| - | <StructureSection load='3h91' size='340' side='right' caption='[[3h91]], [[Resolution|resolution]] 1.50Å' scene=''> | + | <StructureSection load='3h91' size='340' side='right'caption='[[3h91]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3h91]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3H91 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3H91 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3h91]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3H91 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H91 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CBX2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=M3L:N-TRIMETHYLLYSINE'>M3L</scene></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=3h91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h91 OCA], [http://pdbe.org/3h91 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3h91 RCSB], [http://www.ebi.ac.uk/pdbsum/3h91 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3h91 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=3h91 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h91 OCA], [https://pdbe.org/3h91 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h91 RCSB], [https://www.ebi.ac.uk/pdbsum/3h91 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h91 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CBX2_HUMAN CBX2_HUMAN]] Defects in CBX2 are the cause of 46,XY sex reversal type 5 (SRXY5) [MIM:[http://omim.org/entry/613080 613080]]. It is a disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.<ref>PMID:19361780</ref> | + | [https://www.uniprot.org/uniprot/CBX2_HUMAN CBX2_HUMAN] Defects in CBX2 are the cause of 46,XY sex reversal type 5 (SRXY5) [MIM:[https://omim.org/entry/613080 613080]. It is a disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.<ref>PMID:19361780</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CBX2_HUMAN CBX2_HUMAN]] Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Involved in sexual development, acting as activator of NR5A1 expression.<ref>PMID:19361780</ref> <ref>PMID:21282530</ref> | + | [https://www.uniprot.org/uniprot/CBX2_HUMAN CBX2_HUMAN] Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Involved in sexual development, acting as activator of NR5A1 expression.<ref>PMID:19361780</ref> <ref>PMID:21282530</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h9/3h91_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h9/3h91_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Amaya, M F]] | + | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Bochkarev, A]] | + | [[Category: Amaya MF]] |
| - | [[Category: Bountra, C]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Bochkarev A]] |
| - | [[Category: Kozieradzki, I]] | + | [[Category: Bountra C]] |
| - | [[Category: Loppnau, P]] | + | [[Category: Edwards AM]] |
| - | [[Category: Min, J]] | + | [[Category: Kozieradzki I]] |
| - | [[Category: Ouyang, H]] | + | [[Category: Loppnau P]] |
| - | [[Category: Ravichandran, M]] | + | [[Category: Min J]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Ouyang H]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Ravichandran M]] |
| - | [[Category: Cbx2]]
| + | [[Category: Weigelt J]] |
| - | [[Category: Chromatin regulator]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: H3k27]]
| + | |
| - | [[Category: Human chromobox homolog 2]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Repressor]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| Structural highlights
Disease
CBX2_HUMAN Defects in CBX2 are the cause of 46,XY sex reversal type 5 (SRXY5) [MIM:613080. It is a disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females.[1]
Function
CBX2_HUMAN Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Involved in sexual development, acting as activator of NR5A1 expression.[2] [3]
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 PubMed
The eight mammalian Cbx proteins are chromodomain-containing proteins involved in regulation of heterochromatin, gene expression, and developmental programs. They are evolutionarily related to the Drosophila HP1 (dHP1) and Pc (dPc) proteins that are key components of chromatin-associated complexes capable of recognizing repressive marks such as trimethylated Lys-9 and Lys-27, respectively, on histone H3. However, the binding specificity and function of the human homologs, Cbx1-8, remain unclear. To this end we employed structural, biophysical, and mutagenic approaches to characterize the molecular determinants of sequence contextual methyllysine binding to human Cbx1-8 proteins. Although all three human HP1 homologs (Cbx1, -3, -5) replicate the structural and binding features of their dHP counterparts, the five Pc homologs (Cbx2, -4, -6, -7, -8) bind with lower affinity to H3K9me3 or H3K27me3 peptides and are unable to distinguish between these two marks. Additionally, peptide permutation arrays revealed a greater sequence tolerance within the Pc family and suggest alternative nonhistone sequences as potential binding targets for this class of chromodomains. Our structures explain the divergence of peptide binding selectivity in the Pc subfamily and highlight previously unrecognized features of the chromodomain that influence binding and specificity.
Recognition and specificity determinants of the human cbx chromodomains.,Kaustov L, Ouyang H, Amaya M, Lemak A, Nady N, Duan S, Wasney GA, Li Z, Vedadi M, Schapira M, Min J, Arrowsmith CH J Biol Chem. 2011 Jan 7;286(1):521-9. Epub 2010 Nov 3. PMID:21047797[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ. Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene. Am J Hum Genet. 2009 May;84(5):658-63. doi: 10.1016/j.ajhg.2009.03.016. Epub 2009, Apr 9. PMID:19361780 doi:10.1016/j.ajhg.2009.03.016
- ↑ Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ. Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene. Am J Hum Genet. 2009 May;84(5):658-63. doi: 10.1016/j.ajhg.2009.03.016. Epub 2009, Apr 9. PMID:19361780 doi:10.1016/j.ajhg.2009.03.016
- ↑ Vandamme J, Volkel P, Rosnoblet C, Le Faou P, Angrand PO. Interaction proteomics analysis of polycomb proteins defines distinct PRC1 complexes in mammalian cells. Mol Cell Proteomics. 2011 Apr;10(4):M110.002642. doi: 10.1074/mcp.M110.002642., Epub 2011 Jan 31. PMID:21282530 doi:10.1074/mcp.M110.002642
- ↑ Kaustov L, Ouyang H, Amaya M, Lemak A, Nady N, Duan S, Wasney GA, Li Z, Vedadi M, Schapira M, Min J, Arrowsmith CH. Recognition and specificity determinants of the human cbx chromodomains. J Biol Chem. 2011 Jan 7;286(1):521-9. Epub 2010 Nov 3. PMID:21047797 doi:10.1074/jbc.M110.191411
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