title: Crystal structure of the C-terminal domain of human DPY-30-like protein: A component of the histone methyltransferase complex.
abstract: The conserved DPY-30 is an essential component of the dosage compensation complex that balances the X-linked gene expression by regulation of the complex formation in Caenorhabditis elegans. The human DPY-30-like protein (DPY-30L) homolog is a conserved member of certain histone methyltransferase (HMT) complexes. In the human MLL1 (mixed-lineage leukemia-1) HMT complex, DPY-30L binds to the BRE2 homolog ASH2L in order to regulate histone 3-lysine 4 trimethylation. We have determined the 1.2-A crystal structure of the human DPY-30L C-terminal domain (DPY-30L(C)). The DPY-30L(C) structure, harboring the conserved DPY-30 motif, is composed of two alpha-helices linked by a sharp loop and forms a typical X-type four-helix bundle required for dimer formation. DPY-30L(C) dimer formation is largely mediated by an extensive hydrophobic interface with some additional polar interactions. The oligomerization of DPY-30L(C) in solution, together with its reported binding to ASH2L, leads us to propose that the hydrophobic surface of the dimer may provide a platform for interaction with ASH2L in the MLL1 HMT complex.
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.
authors.forename: Xianping
authors.initials: X
authors.lastname: Wang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lou
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Dong
authors.forename: Wen
authors.initials: W
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Peng
authors.forename: Bin
authors.initials: B
authors.lastname: Yin
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Gong
authors.forename: Jiangang
authors.initials: J
authors.lastname: Yuan
authors.forename: Weihong
authors.initials: W
authors.lastname: Zhou
authors.forename: Mark
authors.initials: M
authors.lastname: Bartlam
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Peng
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014157:Transcription Factors
chemical_list: C507432:DPY30 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors