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| | ==Crystal structure of the complex of human chromobox homolog 5 (CBX5) with H3K9(me)3 peptide== | | ==Crystal structure of the complex of human chromobox homolog 5 (CBX5) with H3K9(me)3 peptide== |
| - | <StructureSection load='3fdt' size='340' side='right' caption='[[3fdt]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3fdt' size='340' side='right'caption='[[3fdt]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fdt]] is a 2 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=3FDT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FDT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fdt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FDT 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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CBX5, HP1A ([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=3fdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fdt OCA], [http://pdbe.org/3fdt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fdt RCSB], [http://www.ebi.ac.uk/pdbsum/3fdt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fdt 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=3fdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fdt OCA], [https://pdbe.org/3fdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fdt RCSB], [https://www.ebi.ac.uk/pdbsum/3fdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fdt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CBX5_HUMAN CBX5_HUMAN]] Component of heterochromatin that recognizes and binds histone H3 tails methylated at 'Lys-9' (H3K9me), leading to epigenetic repression. In contrast, it is excluded from chromatin when 'Tyr-41' of histone H3 is phosphorylated (H3Y41ph). Can interact with lamin-B receptor (LBR). This interaction can contribute to the association of the heterochromatin with the inner nuclear membrane. Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins.<ref>PMID:19783980</ref> | + | [https://www.uniprot.org/uniprot/CBX5_HUMAN CBX5_HUMAN] Component of heterochromatin that recognizes and binds histone H3 tails methylated at 'Lys-9' (H3K9me), leading to epigenetic repression. In contrast, it is excluded from chromatin when 'Tyr-41' of histone H3 is phosphorylated (H3Y41ph). Can interact with lamin-B receptor (LBR). This interaction can contribute to the association of the heterochromatin with the inner nuclear membrane. Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins.<ref>PMID:19783980</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/fd/3fdt_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fd/3fdt_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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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: Synthetic construct]] |
| - | [[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: Cbx5]]
| + | [[Category: Weigelt J]] |
| - | [[Category: Centromere]]
| + | |
| - | [[Category: Chromobox homolog5]]
| + | |
| - | [[Category: Chromosomal protein]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Nucleosome core]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Sgc]]
| + | |
| Structural highlights
Function
CBX5_HUMAN Component of heterochromatin that recognizes and binds histone H3 tails methylated at 'Lys-9' (H3K9me), leading to epigenetic repression. In contrast, it is excluded from chromatin when 'Tyr-41' of histone H3 is phosphorylated (H3Y41ph). Can interact with lamin-B receptor (LBR). This interaction can contribute to the association of the heterochromatin with the inner nuclear membrane. Involved in the formation of functional kinetochore through interaction with MIS12 complex proteins.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dawson MA, Bannister AJ, Gottgens B, Foster SD, Bartke T, Green AR, Kouzarides T. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature. 2009 Oct 8;461(7265):819-22. doi: 10.1038/nature08448. Epub 2009 Sep 27. PMID:19783980 doi:10.1038/nature08448
- ↑ 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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