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| | <StructureSection load='6pa7' size='340' side='right'caption='[[6pa7]], [[Resolution|resolution]] 2.94Å' scene=''> | | <StructureSection load='6pa7' size='340' side='right'caption='[[6pa7]], [[Resolution|resolution]] 2.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6pa7]] is a 14 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PA7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PA7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6pa7]] is a 14 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] 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=6PA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PA7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.94Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DNMT3A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DNMT3B ([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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_(cytosine-5-)-methyltransferase DNA (cytosine-5-)-methyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.37 2.1.1.37] </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=6pa7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pa7 OCA], [https://pdbe.org/6pa7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pa7 RCSB], [https://www.ebi.ac.uk/pdbsum/6pa7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pa7 ProSAT]</span></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=6pa7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pa7 OCA], [http://pdbe.org/6pa7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pa7 RCSB], [http://www.ebi.ac.uk/pdbsum/6pa7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pa7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/DNM3B_HUMAN DNM3B_HUMAN]] ICF syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:10647011</ref> <ref>PMID:10555141</ref> <ref>PMID:10588719</ref> <ref>PMID:11102980</ref> <ref>PMID:15580563</ref> | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/H2A1_XENLA H2A1_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [[http://www.uniprot.org/uniprot/DNM3A_HUMAN DNM3A_HUMAN]] Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZNF238. Can actively repress transcription through the recruitment of HDAC activity (By similarity).<ref>PMID:16357870</ref> [[http://www.uniprot.org/uniprot/H4_XENLA H4_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [[http://www.uniprot.org/uniprot/DNM3B_HUMAN DNM3B_HUMAN]] Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Function as transcriptional corepressor by associating with ZHX1.<ref>PMID:16357870</ref> <ref>PMID:17303076</ref> <ref>PMID:18413740</ref> <ref>PMID:18567530</ref> [[http://www.uniprot.org/uniprot/H32_XENLA H32_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [[http://www.uniprot.org/uniprot/H2B11_XENLA H2B11_XENLA]] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. | + | [https://www.uniprot.org/uniprot/H4_XENLA H4_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | CpG methylation by de novo DNA methyltransferases (DNMTs) 3A and 3B is essential for mammalian development and differentiation and is frequently dysregulated in cancer(1). These two DNMTs preferentially bind to nucleosomes, yet cannot methylate the DNA wrapped around the nucleosome core(2), and they favour the methylation of linker DNA at positioned nucleosomes(3,4). Here we present the cryo-electron microscopy structure of a ternary complex of catalytically competent DNMT3A2, the catalytically inactive accessory subunit DNMT3B3 and a nucleosome core particle flanked by linker DNA. The catalytic-like domain of the accessory DNMT3B3 binds to the acidic patch of the nucleosome core, which orients the binding of DNMT3A2 to the linker DNA. The steric constraints of this arrangement suggest that nucleosomal DNA must be moved relative to the nucleosome core for de novo methylation to occur.
| + | |
| - | | + | |
| - | Structure of nucleosome-bound DNA methyltransferases DNMT3A and DNMT3B.,Xu TH, Liu M, Zhou XE, Liang G, Zhao G, Xu HE, Melcher K, Jones PA Nature. 2020 Oct;586(7827):151-155. doi: 10.1038/s41586-020-2747-1. Epub 2020 Sep, 23. PMID:32968275<ref>PMID:32968275</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6pa7" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]] | | *[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]] |
| | *[[Histone 3D structures|Histone 3D structures]] | | *[[Histone 3D structures|Histone 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: African clawed frog]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jones, P A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Liang, G]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Liu, M]] | + | [[Category: Jones PA]] |
| - | [[Category: Melcher, K]] | + | [[Category: Liang G]] |
| - | [[Category: Xu, H E]] | + | [[Category: Liu M]] |
| - | [[Category: Xu, T H]] | + | [[Category: Melcher K]] |
| - | [[Category: Zhao, G]] | + | [[Category: Xu HE]] |
| - | [[Category: Zhou, X E]] | + | [[Category: Xu TH]] |
| - | [[Category: Complex]] | + | [[Category: Zhao G]] |
| - | [[Category: Methyltransferase]] | + | [[Category: Zhou XE]] |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-dna complex]]
| + | |
