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	Cryo-EM structure of SETD2/Set2 methyltransferase bound to a nucleosome containing oncohistone mutations.
Journal, issue, pages	Cell Discov, Vol. 7, Issue 1, Page 32, Year 2021
Publish date	May 11, 2021
Authors	Yingying Liu / Yanjun Zhang / Han Xue / Mi Cao / Guohui Bai / Zongkai Mu / Yanli Yao / Shuyang Sun / Dong Fang / Jing Huang /
PubMed Abstract	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 ...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.
External links	Cell Discov / PubMed:33972509 / PubMed Central
Methods	EM (single particle)
Resolution	3.1 - 3.7 Å
Structure data	31039 7ea5 EMDB-31039, PDB-7ea5: Yeast Set2 bound to a nucleosome containing oncohistone mutations Method: EM (single particle) / Resolution: 3.3 Å 31040 7ea8 EMDB-31040, PDB-7ea8: Human SETD2 bound to a nucleosome containing oncohistone mutations Method: EM (single particle) / Resolution: 3.1 Å EMDB-31041: Human SETD2 bound to wild-type nucleosome Method: EM (single particle) / Resolution: 3.7 Å EMDB-31042: Yeast Set2 bound to wild-type nucleosome Method: EM (single particle) / Resolution: 3.3 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-SAM: S-ADENOSYLMETHIONINE
Source	xenopus laevis (African clawed frog) saccharomyces cerevisiae (brewer's yeast) synthetic construct (others) homo sapiens (human)
Keywords	GENE REGULATION / methyltransferase / Set2 / nucleosome / H3K36M mutation / SETD2 / H3.3K36M