Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Molecular basis of nucleosomal H3K36 methylation by NSD methyltransferases.
Journal, issue, pages	Nature, Vol. 590, Issue 7846, Page 498-503, Year 2021
Publish date	Dec 23, 2020
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 /
PubMed 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.
External links	Nature / PubMed:33361816 / PubMed Central
Methods	EM (single particle)
Resolution	3.15 - 3.75 Å
Structure data	30453 7cro EMDB-30453, PDB-7cro: NSD2 bearing E1099K/T1150A dual mutation in complex with 187-bp NCP Method: EM (single particle) / Resolution: 3.75 Å EMDB-30454: NSD3 bearing E1181K/T1232A dual mutation in complex with 187-bp NCP (class2 map) Method: EM (single particle) / Resolution: 3.24 Å 30455 7crp EMDB-30455, PDB-7crp: NSD3 bearing E1181K/T1232A dual mutation in complex with 187-bp NCP (1:1 binding mode) Method: EM (single particle) / Resolution: 3.2 Å 30456 7crq EMDB-30456, PDB-7crq: NSD3 bearing E1181K/T1232A dual mutation in complex with 187-bp NCP (2:1 binding mode) Method: EM (single particle) / Resolution: 3.15 Å 30457 7crr EMDB-30457, PDB-7crr: Native NSD3 bound to 187-bp nucleosome Method: EM (single particle) / Resolution: 3.48 Å
Chemicals	ChemComp-SAM: S-ADENOSYLMETHIONINE ChemComp-ZN: Unknown entry
Source	xenopus laevis (African clawed frog) homo sapiens (human) xenopus tropicalis (tropical clawed frog) synthetic construct (others)
Keywords	GENE REGULATION / nucleosome complex / histone methyltransferase / DNA / nucleosome complex histone methyltransferase / Gene reguration