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| | ==Structural model of Set8 histone H4 Lys20 methyltransferase bound to nucleosome core particle== | | ==Structural model of Set8 histone H4 Lys20 methyltransferase bound to nucleosome core particle== |
| - | <StructureSection load='5hq2' size='340' side='right' caption='[[5hq2]], [[Resolution|resolution]] 4.50Å' scene=''> | + | <StructureSection load='5hq2' size='340' side='right'caption='[[5hq2]], [[Resolution|resolution]] 4.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hq2]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HQ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HQ2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hq2]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C], [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=5HQ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HQ2 FirstGlance]. <br> |
| - | </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=5hq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hq2 OCA], [http://pdbe.org/5hq2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hq2 RCSB], [http://www.ebi.ac.uk/pdbsum/5hq2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hq2 ProSAT]</span></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]] 4.5Å</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=5hq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hq2 OCA], [https://pdbe.org/5hq2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hq2 RCSB], [https://www.ebi.ac.uk/pdbsum/5hq2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hq2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RCC1_YEAST RCC1_YEAST]] Guanine nucleotide exchange factor that promotes the exchange of GSP1/GSP2-bound GDP by GTP and controls RNA metabolism and transport. Involved in yeast pheromone response pathway and in mRNA metabolism. Involved in nuclear pore complex (NPC) assembly and required for mRNA and ribosome nuclear export. Binds chromatin and is involved NPC-mediated transcriptional control.<ref>PMID:2548085</ref> <ref>PMID:2277633</ref> <ref>PMID:1666302</ref> <ref>PMID:1865879</ref> <ref>PMID:1398069</ref> <ref>PMID:7679070</ref> <ref>PMID:8070652</ref> <ref>PMID:9971735</ref> <ref>PMID:11071906</ref> <ref>PMID:11142374</ref> <ref>PMID:11509570</ref> <ref>PMID:11589573</ref> <ref>PMID:12654904</ref> <ref>PMID:16365162</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/SETD8_HUMAN SETD8_HUMAN]] Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes.<ref>PMID:12086618</ref> <ref>PMID:12121615</ref> <ref>PMID:15200950</ref> <ref>PMID:16517599</ref> <ref>PMID:17707234</ref> <ref>PMID:15933069</ref> <ref>PMID:15933070</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/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. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Set8 is the only mammalian monomethyltransferase responsible for H4K20me1, a methyl mark critical for genomic integrity of eukaryotic cells. We present here a structural model for how Set8 uses multivalent interactions to bind and methylate the nucleosome based on crystallographic and solution studies of the Set8/nucleosome complex. Our studies indicate that Set8 employs its i-SET and c-SET domains to engage nucleosomal DNA 1 to 1.5 turns from the nucleosomal dyad and in doing so, it positions the SET domain for catalysis with H4 Lys20. Surprisingly, we find that a basic N-terminal extension to the SET domain plays an even more prominent role in nucleosome binding, possibly by making an arginine anchor interaction with the nucleosome H2A/H2B acidic patch. We further show that proliferating cell nuclear antigen and the nucleosome compete for binding to Set8 through this basic extension, suggesting a mechanism for how nucleosome binding protects Set8 from proliferating cell nuclear antigen-dependent degradation during the cell cycle.
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| - | Multivalent Interactions by the Set8 Histone Methyltransferase With Its Nucleosome Substrate.,Girish TS, McGinty RK, Tan S J Mol Biol. 2016 Apr 24;428(8):1531-43. doi: 10.1016/j.jmb.2016.02.025. Epub 2016, Mar 4. PMID:26953260<ref>PMID:26953260</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5hq2" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
| - | *[[Histone|Histone]] | + | *[[Histone 3D structures|Histone 3D structures]] |
| - | *[[Histone methyltransferase|Histone methyltransferase]] | + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: McGinty, R K]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Tan, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Tavarekere, G]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Chromatin complex]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Chromatin enzyme]] | + | [[Category: Xenopus laevis]] |
| - | [[Category: Epigenetic]] | + | [[Category: McGinty RK]] |
| - | [[Category: Histone methyltransferase]] | + | [[Category: Tan S]] |
| - | [[Category: Transferase-dna complex]] | + | [[Category: Tavarekere G]] |
