View source for 7cro


==NSD2 bearing E1099K/T1150A dual mutation in complex with 187-bp NCP==
<StructureSection load='7cro' size='340' side='right'caption='[[7cro]], [[Resolution|resolution]] 3.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7cro]] is a 11 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/Xenopus_tropicalis Xenopus tropicalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CRO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CRO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene>, <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=7cro FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cro OCA], [https://pdbe.org/7cro PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cro RCSB], [https://www.ebi.ac.uk/pdbsum/7cro PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cro ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Histone methyltransferases of the nuclear receptor-binding SET domain protein (NSD) family, including NSD1, NSD2 and NSD3, have crucial roles in chromatin regulation and are implicated in oncogenesis(1,2). NSD enzymes exhibit an autoinhibitory state that is relieved by binding to nucleosomes, enabling dimethylation of histone H3 at Lys36 (H3K36)(3-7). However, the molecular basis that underlies this mechanism is largely unknown. Here we solve the cryo-electron microscopy structures of NSD2 and NSD3 bound to mononucleosomes. We find that binding of NSD2 and NSD3 to mononucleosomes causes DNA near the linker region to unwrap, which facilitates insertion of the catalytic core between the histone octamer and the unwrapped segment of DNA. A network of DNA- and histone-specific contacts between NSD2 or NSD3 and the nucleosome precisely defines the position of the enzyme on the nucleosome, explaining the specificity of methylation to H3K36. Intermolecular contacts between NSD proteins and nucleosomes are altered by several recurrent cancer-associated mutations in NSD2 and NSD3. NSDs that contain these mutations are catalytically hyperactive in vitro and in cells, and their ectopic expression promotes the proliferation of cancer cells and the growth of xenograft tumours. Together, our research provides molecular insights into the nucleosome-based recognition and histone-modification mechanisms of NSD2 and NSD3, which could lead to strategies for therapeutic targeting of proteins of the NSD family.

Molecular basis of nucleosomal H3K36 methylation by NSD methyltransferases.,Li W, Tian W, Yuan G, Deng P, Sengupta D, Cheng Z, Cao Y, Ren J, Qin Y, Zhou Y, Jia Y, Gozani O, Patel DJ, Wang Z Nature. 2021 Feb;590(7846):498-503. doi: 10.1038/s41586-020-03069-8. Epub 2020 , Dec 23. PMID:33361816<ref>PMID:33361816</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7cro" style="background-color:#fffaf0;"></div>

==See Also==
*[[Histone 3D structures|Histone 3D structures]]
*[[Histone methyltransferase 3D structures|Histone methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Xenopus laevis]]
[[Category: Xenopus tropicalis]]
[[Category: Deng P]]
[[Category: Gozani O]]
[[Category: Li W]]
[[Category: Patel D]]
[[Category: Tian W]]
[[Category: Wang Z]]
[[Category: Yuan G]]