6ict | pdb_00006ict
Structure of SETD3 bound to SAH and methylated actin
Structural highlights
FunctionSETD3_HUMAN Histone methyltransferase that methylates 'Lys-36' of histone H3 (H3K36me). H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation (By similarity). Publication Abstract from PubMedSETD3 is a member of the SET (Su(var)3-9, Enhancer of zeste, and Trithorax) domain protein superfamily and plays important roles in hypoxic pulmonary hypertension, muscle differentiation, and carcinogenesis. Previously, we identified SETD3 as the actin-specific methyltransferase that methylates the N3 of His73 on beta-actin (Kwiatkowski et al., 2018). Here, we present two structures of S-adenosyl-L-homocysteine-bound SETD3 in complex with either an unmodified beta-actin peptide or its His-methylated variant. Structural analyses, supported by biochemical experiments and enzyme activity assays, indicate that the recognition and methylation of beta-actin by SETD3 are highly sequence specific, and that both SETD3 and beta-actin adopt pronounced conformational changes upon binding to each other. In conclusion, this study is the first to show a catalytic mechanism of SETD3-mediated histidine methylation on beta-actin, which not only throws light on the protein histidine methylation phenomenon but also facilitates the design of small molecule inhibitors of SETD3. Structural insights into SETD3-mediated histidine methylation on beta-actin.,Guo Q, Liao S, Kwiatkowski S, Tomaka W, Yu H, Wu G, Tu X, Min J, Drozak J, Xu C Elife. 2019 Feb 20;8. pii: 43676. doi: 10.7554/eLife.43676. PMID:30785395[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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