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| | <StructureSection load='6v2s' size='340' side='right'caption='[[6v2s]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='6v2s' size='340' side='right'caption='[[6v2s]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6v2s]] 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=6V2S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V2S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6v2s]] is a 4 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=6V2S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V2S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</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]] 1.6Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5R0:4-~{TERT}-BUTYLBENZOIC+ACID'>5R0</scene>, <scene name='pdbligand=5R5:METHYL+(2~{S})-2-AZANYL-3-OXIDANYL-PROPANOATE'>5R5</scene>, <scene name='pdbligand=ELY:N~6~,N~6~-DIETHYL-L-LYSINE'>ELY</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5R0:4-~{TERT}-BUTYLBENZOIC+ACID'>5R0</scene>, <scene name='pdbligand=5R5:METHYL+(2~{S})-2-AZANYL-3-OXIDANYL-PROPANOATE'>5R5</scene>, <scene name='pdbligand=ELY:N~6~,N~6~-DIETHYL-L-LYSINE'>ELY</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3r93|3r93]]</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=6v2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v2s OCA], [https://pdbe.org/6v2s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v2s RCSB], [https://www.ebi.ac.uk/pdbsum/6v2s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v2s ProSAT]</span></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'>[http://proteopedia.org/fgij/fg.htm?mol=6v2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v2s OCA], [http://pdbe.org/6v2s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v2s RCSB], [http://www.ebi.ac.uk/pdbsum/6v2s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v2s 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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Bountra, C]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Bountra C]] |
| - | [[Category: Liu, Y]] | + | [[Category: Edwards AM]] |
| - | [[Category: Min, J]] | + | [[Category: Liu Y]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Min J]] |
| - | [[Category: Tempel, W]] | + | [[Category: Tempel W]] |
| - | [[Category: Walker, J R]] | + | [[Category: Walker JR]] |
| - | [[Category: Gene regulation]]
| + | |
| - | [[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]
Publication Abstract from PubMed
The CDY (chromodomain on the Y) proteins play an essential role in normal spermatogenesis and brain development. Dysregulation of their expression has been linked to male infertility and various neurological diseases. Like the chromodomains of HP1 and Polycomb, the CDY chromodomains also recognize the lysine-methylated ARKS motif embedded in histone and non-histone proteins. Interestingly, the CDY chromodomains exhibit different binding preferences for the lysine-methylated ARKS motif in different sequence contexts. Here, we present the structural basis for selective binding of CDY1 to H3K9me3 and preferential binding of CDYL2 to H3tK27me3 over H3K27me3. In addition, we use a CDYL1/2-selective compound, UNC4850, to gain further insight into the molecular mechanisms underlying CDYL2 binding specificity. Our work also provides critical implications that CDYL1b's role in the regulation of neural development is dependent on its recognition of the lysine-methylated ARKS motif.
Structural Basis for the Binding Selectivity of Human CDY Chromodomains.,Dong C, Liu Y, Lyu TJ, Beldar S, Lamb KN, Tempel W, Li Y, Li Z, James LI, Qin S, Wang Y, Min J Cell Chem Biol. 2020 May 26. pii: S2451-9456(20)30153-7. doi:, 10.1016/j.chembiol.2020.05.007. PMID:32470319[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
- ↑ Dong C, Liu Y, Lyu TJ, Beldar S, Lamb KN, Tempel W, Li Y, Li Z, James LI, Qin S, Wang Y, Min J. Structural Basis for the Binding Selectivity of Human CDY Chromodomains. Cell Chem Biol. 2020 May 26. pii: S2451-9456(20)30153-7. doi:, 10.1016/j.chembiol.2020.05.007. PMID:32470319 doi:http://dx.doi.org/10.1016/j.chembiol.2020.05.007
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