5jlb
Crystal structure of SETD2 bound to histone H3.3 K36I peptideCrystal structure of SETD2 bound to histone H3.3 K36I peptide
Structural highlights
FunctionSETD2_HUMAN Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.[1] Publication Abstract from PubMedHigh-frequency point mutations of genes encoding histones have been identified recently as novel drivers in a number of tumors. Specifically, the H3K36M/I mutations were shown to be oncogenic in chondroblastomas and undifferentiated sarcomas by inhibiting H3K36 methyltransferases, including SETD2. Here we report the crystal structures of the SETD2 catalytic domain bound to H3K36M or H3K36I peptides with SAH (S-adenosylhomocysteine). In the complex structure, the catalytic domain adopts an open conformation, with the K36M/I peptide snuggly positioned in a newly formed substrate channel. Our structural and biochemical data reveal the molecular basis underying oncohistone recognition by and inhibition of SETD2. Molecular basis for oncohistone H3 recognition by SETD2 methyltransferase.,Yang S, Zheng X, Lu C, Li GM, Allis CD, Li H Genes Dev. 2016 Jul 15;30(14):1611-6. doi: 10.1101/gad.284323.116. PMID:27474439[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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