title: Structural basis of the recognition of a methylated histone tail by JMJD2A.
abstract: The Jumonji C domain is a catalytic motif that mediates histone lysine demethylation. The Jumonji C-containing oxygenase JMJD2A specifically demethylates tri- and dimethylated lysine-9 and lysine-36 of histone 3 (H3K9/36 me3/2). Here we present structures of the JMJD2A catalytic core complexed with methylated H3K36 peptide substrates in the presence of Fe(II) and N-oxalylglycine. We found that the interaction between JMJD2A and peptides largely involves the main chains of the enzyme and the peptide. The peptide-binding specificity is primarily determined by the primary structure of the peptide, which explains the specificity of JMJD2A for methylated H3K9 and H3K36 instead of other methylated residues such as H3K27. The specificity for a particular methyl group, however, is affected by multiple factors, such as space and the electrostatic environment in the catalytic center of the enzyme. These results provide insights into the mechanisms and specificity of histone demethylation.
authors.affiliation: Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Zhongzhou
authors.initials: Z
authors.lastname: Chen
authors.forename: Jianye
authors.initials: J
authors.lastname: Zang
authors.forename: John
authors.initials: J
authors.lastname: Kappler
authors.forename: Xia
authors.initials: X
authors.lastname: Hong
authors.forename: Frances
authors.initials: F
authors.lastname: Crawford
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Lan
authors.forename: Chengyu
authors.initials: C
authors.lastname: Jiang
authors.forename: Johnathan
authors.initials: J
authors.lastname: Whetstine
authors.forename: Shaodong
authors.initials: S
authors.lastname: Dai
authors.forename: Kirk
authors.initials: K
authors.lastname: Hansen
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Gongyi
authors.initials: G
authors.lastname: Zhang
mesh_terms: D001426:Bacterial Proteins; D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D008745:Methylation; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D015008:Yersinia enterocolitica / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D006657:Histones; D010089:Oxidoreductases, N-Demethylating