title: Structure of human MRG15 chromo domain and its binding to Lys36-methylated histone H3.
abstract: Human MRG15 is a transcription factor that plays a vital role in embryonic development, cell proliferation and cellular senescence. It comprises a putative chromo domain in the N-terminal part that has been shown to participate in chromatin remodeling and transcription regulation. We report here the crystal structure of human MRG15 chromo domain at 2.2 A resolution. The MRG15 chromo domain consists of a beta-barrel and a long alpha-helix and assumes a structure more similar to the Drosophila MOF chromo barrel domain than the typical HP1/Pc chromo domains. The beta-barrel core contains a hydrophobic pocket formed by three conserved aromatic residues Tyr26, Tyr46 and Trp49 as a potential binding site for a modified residue of histone tail. However, the binding groove for the histone tail seen in the HP1/Pc chromo domains is pre-occupied by an extra beta-strand. In vitro binding assay results indicate that the MRG15 chromo domain can bind to methylated Lys36, but not methylated Lys4, Lys9 and Lys27 of histone H3. These data together suggest that the MRG15 chromo domain may function as an adaptor module which can bind to a modified histone H3 in a mode different from that of the HP1/Pc chromo domains.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Jiamu
authors.initials: J
authors.lastname: Du
authors.forename: Bingfa
authors.initials: B
authors.lastname: Sun
authors.forename: Xianchi
authors.initials: X
authors.lastname: Dong
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xu
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Zhou
authors.forename: Qingqiu
authors.initials: Q
authors.lastname: Huang
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
authors.forename: Jianping
authors.initials: J
authors.lastname: Ding
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006657:Histones; C470833:MORF4L1 protein, human; D014157:Transcription Factors; D008239:Lysine