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- EMDB-30453: NSD2 bearing E1099K/T1150A dual mutation in complex with 187-bp NCP -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30453 | |||||||||||||||||||||
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Title | NSD2 bearing E1099K/T1150A dual mutation in complex with 187-bp NCP | |||||||||||||||||||||
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![]() | NSD2 bearing E1099K/T1150A dual mutation in complex with 187-bp NCP: Histone H3, H4, H2A and H2B ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||||||||||||||
Function / homology | ![]() atrial septum secundum morphogenesis / dermal bone morphogenesis / fin development / [histone H3]-lysine36 N-dimethyltransferase / histone methyltransferase activity (H4-K20 specific) / regulation of double-strand break repair via nonhomologous end joining / atrial septum primum morphogenesis / positive regulation of isotype switching to IgA isotypes / regulation of establishment of protein localization / membranous septum morphogenesis ...atrial septum secundum morphogenesis / dermal bone morphogenesis / fin development / [histone H3]-lysine36 N-dimethyltransferase / histone methyltransferase activity (H4-K20 specific) / regulation of double-strand break repair via nonhomologous end joining / atrial septum primum morphogenesis / positive regulation of isotype switching to IgA isotypes / regulation of establishment of protein localization / membranous septum morphogenesis / histone methyltransferase activity (H3-K36 specific) / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() ![]() | |||||||||||||||||||||
Method | ![]() ![]() | |||||||||||||||||||||
![]() | Li W / Tian W / Yuan G / Deng P / Gozani O / Patel D / Wang Z | |||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Molecular basis of nucleosomal H3K36 methylation by NSD methyltransferases. Authors: Wanqiu Li / Wei Tian / Gang Yuan / Pujuan Deng / Deepanwita Sengupta / Zhongjun Cheng / Yinghua Cao / Jiahao Ren / Yan Qin / Yuqiao Zhou / Yulin Jia / Or Gozani / Dinshaw J Patel / Zhanxin Wang / ![]() ![]() Abstract: 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. ...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. NSD enzymes exhibit an autoinhibitory state that is relieved by binding to nucleosomes, enabling dimethylation of histone H3 at Lys36 (H3K36). 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. | |||||||||||||||||||||
Validation Report | PDB-ID: 7cro![]() ![]() ![]() | |||||||||||||||||||||
History |
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Structure visualization
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
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Download
Header (meta data in XML format) |
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Images |
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Archive directory |
-Related structure data
Related structure data | ![]() 7croCM ![]() 7crpC ![]() 7crqC ![]() 7crrC C: citing same article ( M: atomic model generated by this map |
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Similar-shape strucutres |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire NSD2 bearing E1099K/T1150A dual mutation in complex with 187-bp NCP
+Component #1: protein, NSD2 bearing E1099K/T1150A dual mutation in complex with...
+Component #2: protein, Histone H3, H4, H2A and H2B
+Component #3: protein, DNA
+Component #4: protein, NSD2
+Component #5: protein, Histone H3
+Component #6: protein, Histone H4
+Component #7: protein, Histone H2A
+Component #8: protein, Histone H2B
+Component #9: nucleic-acid, DNA (168-MER)
+Component #10: nucleic-acid, DNA (168-MER)
+Component #11: protein, Histone-lysine N-methyltransferase NSD2
+Component #12: ligand, S-ADENOSYLMETHIONINE
+Component #13: ligand, ZINC ION
-Experimental details
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Sample preparation
Specimen | Specimen state: Particle / Method: ![]() |
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Sample solution | Specimen conc.: 0.3 mg/mL / pH: 7.5 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Temperature: 281 K / Humidity: 100 % Details: blotted for 3 s before being plunged into liquid ethane. |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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![]() | Microscope: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN![]() |
Lens | Cs: 2.7 mm / Imaging mode: BRIGHT FIELD![]() |
Specimen Holder | Model: FEI TITAN KRIOS AUTOGRID HOLDER |
Camera | Detector: GATAN K2 SUMMIT (4k x 4k) |
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Image processing
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3D reconstruction | Resolution: 3.75 Å / Resolution method: FSC 0.143 CUT-OFF |
-Atomic model buiding
Output model |
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