7ea5
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Yeast Set2 bound to a nucleosome containing oncohistone mutations== |
| - | <StructureSection load='7ea5' size='340' side='right'caption='[[7ea5]]' scene=''> | + | <StructureSection load='7ea5' size='340' side='right'caption='[[7ea5]], [[Resolution|resolution]] 3.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ea5]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae], [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=7EA5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EA5 FirstGlance]. <br> |
| - | </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=7ea5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ea5 OCA], [https://pdbe.org/7ea5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ea5 RCSB], [https://www.ebi.ac.uk/pdbsum/7ea5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ea5 ProSAT]</span></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]] 3.3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAM:S-ADENOSYLMETHIONINE'>SAM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=7ea5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ea5 OCA], [https://pdbe.org/7ea5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ea5 RCSB], [https://www.ebi.ac.uk/pdbsum/7ea5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ea5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Substitution of lysine 36 with methionine in histone H3.3 (H3.3K36M) is an oncogenic mutation that inhibits SETD2-mediated histone H3K36 tri-methylation in tumors. To investigate how the oncohistone mutation affects the function of SETD2 at the nucleosome level, we determined the cryo-EM structure of human SETD2 associated with an H3.3K36M nucleosome and cofactor S-adenosylmethionine (SAM), and revealed that SETD2 is attached to the N-terminal region of histone H3 and the nucleosome DNA at superhelix location 1, accompanied with the partial unwrapping of nucleosome DNA to expose the SETD2-binding site. These structural features were also observed in the previous cryo-EM structure of the fungal Set2-nucleosome complex. By contrast with the stable association of SETD2 with the H3.3K36M nucleosome, the EM densities of SETD2 could not be observed on the wild-type nucleosome surface, suggesting that the association of SETD2 with wild-type nucleosome might be transient. The linker histone H1, which stabilizes the wrapping of nucleosome DNA at the entry/exit sites, exhibits an inhibitory effect on the activities of SETD2 and displays inversely correlated genome distributions with that of the H3K36me3 marks. Cryo-EM analysis of yeast H3K36 methyltransferase Set2 complexed with nucleosomes further revealed evolutionarily conserved structural features for nucleosome recognition in eukaryotes, and provides insights into the mechanism of activity regulation. These findings have advanced our understanding of the structural basis for the tumorigenesis mechanism of the H3.3K36M mutation and highlight the effect of nucleosome conformation on the regulation of histone modification. | ||
| + | |||
| + | Cryo-EM structure of SETD2/Set2 methyltransferase bound to a nucleosome containing oncohistone mutations.,Liu Y, Zhang Y, Xue H, Cao M, Bai G, Mu Z, Yao Y, Sun S, Fang D, Huang J Cell Discov. 2021 May 11;7(1):32. doi: 10.1038/s41421-021-00261-6. PMID:33972509<ref>PMID:33972509</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7ea5" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Histone 3D structures|Histone 3D structures]] | ||
| + | *[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Saccharomyces cerevisiae]] |
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Xenopus laevis]] | ||
| + | [[Category: Jing H]] | ||
| + | [[Category: Liu Y]] | ||
Current revision
Yeast Set2 bound to a nucleosome containing oncohistone mutations
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