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| | ==The crystal structure of MPP8== | | ==The crystal structure of MPP8== |
| - | <StructureSection load='3lwe' size='340' side='right' caption='[[3lwe]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='3lwe' size='340' side='right'caption='[[3lwe]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3lwe]] 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=3LWE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LWE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3lwe]] is a 2 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=3LWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LWE FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3r93|3r93]]</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]] 2.05Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MPHOSPH8, MPP8 ([http://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'>[https://proteopedia.org/fgij/fg.htm?mol=3lwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lwe OCA], [https://pdbe.org/3lwe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lwe RCSB], [https://www.ebi.ac.uk/pdbsum/3lwe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lwe ProSAT]</span></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=3lwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lwe OCA], [http://pdbe.org/3lwe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3lwe RCSB], [http://www.ebi.ac.uk/pdbsum/3lwe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3lwe ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MPP8_HUMAN MPP8_HUMAN]] Involved in transcriptional regulation. Specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene. Mediates down-regulation of CDH1 expression.<ref>PMID:20871592</ref> | + | [https://www.uniprot.org/uniprot/MPP8_HUMAN MPP8_HUMAN] Involved in transcriptional regulation. Specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene. Mediates down-regulation of CDH1 expression.<ref>PMID:20871592</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/lw/3lwe_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lw/3lwe_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: Crombet, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, Z]] | + | [[Category: Crombet L]] |
| - | [[Category: Min, J]] | + | [[Category: Li Z]] |
| - | [[Category: Pan, P W]] | + | [[Category: Min J]] |
| - | [[Category: Ruan, J]] | + | [[Category: Pan PW]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Ruan J]] |
| - | [[Category: Tempel, W]] | + | [[Category: Tempel W]] |
| - | [[Category: Tong, Y]] | + | [[Category: Tong Y]] |
| - | [[Category: Xu, C]] | + | [[Category: Xu C]] |
| - | [[Category: Zang, J]] | + | [[Category: Zang J]] |
| - | [[Category: Ank repeat]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Mpp8]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Sgc]]
| + | |
| Structural highlights
Function
MPP8_HUMAN Involved in transcriptional regulation. Specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene. Mediates down-regulation of CDH1 expression.[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
BACKGROUND: M-phase phosphoprotein 8 (MPP8) was initially identified to be a component of the RanBPM-containing large protein complex, and has recently been shown to bind to methylated H3K9 both in vivo and in vitro. MPP8 binding to methylated H3K9 is suggested to recruit the H3K9 methyltransferases GLP and ESET, and DNA methyltransferase 3A to the promoter of the E-cadherin gene, mediating the E-cadherin gene silencing and promote tumor cell motility and invasion. MPP8 contains a chromodomain in its N-terminus, which is used to bind the methylated H3K9. METHODOLOGY/PRINCIPAL FINDINGS: Here, we reported the crystal structures of human MPP8 chromodomain alone and in complex with the trimethylated histone H3K9 peptide (residue 1-15). The complex structure unveils that the human MPP8 chromodomain binds methylated H3K9 through a conserved recognition mechanism, which was also observed in Drosophila HP1, a chromodomain containing protein that binds to methylated H3K9 as well. The structure also reveals that the human MPP8 chromodomain forms homodimer, which is mediated via an unexpected domain swapping interaction through two beta strands from the two protomer subunits. CONCLUSIONS/SIGNIFICANCE: Our findings reveal the molecular mechanism of selective binding of human MPP8 chromodomain to methylated histone H3K9. The observation of human MPP8 chromodomain in both solution and crystal lattice may provide clues to study MPP8-mediated gene regulation furthermore.
Structural basis for specific binding of human MPP8 chromodomain to histone H3 methylated at lysine 9.,Li J, Li Z, Ruan J, Xu C, Tong Y, Pan PW, Tempel W, Crombet L, Min J, Zang J PLoS One. 2011;6(10):e25104. Epub 2011 Oct 12. PMID:22022377[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kokura K, Sun L, Bedford MT, Fang J. Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene silencing and promotes tumour cell motility and invasion. EMBO J. 2010 Nov 3;29(21):3673-87. doi: 10.1038/emboj.2010.239. Epub 2010 Sep 24. PMID:20871592 doi:http://dx.doi.org/10.1038/emboj.2010.239
- ↑ Li J, Li Z, Ruan J, Xu C, Tong Y, Pan PW, Tempel W, Crombet L, Min J, Zang J. Structural basis for specific binding of human MPP8 chromodomain to histone H3 methylated at lysine 9. PLoS One. 2011;6(10):e25104. Epub 2011 Oct 12. PMID:22022377 doi:10.1371/journal.pone.0025104
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