title: A dimeric viral SET domain methyltransferase specific to Lys27 of histone H3.
abstract: Site-specific lysine methylation of histones by SET domains is a hallmark for epigenetic control of gene transcription in eukaryotic organisms. Here we report that a SET domain protein from Paramecium bursaria chlorella virus can specifically di-methylate Lys27 in histone H3, a modification implicated in gene silencing. The solution structure of the viral SET domain reveals a butterfly-shaped head-to-head symmetric dimer different from other known protein methyltransferases. Each subunit consists of a Greek-key antiparallel beta-barrel and a three-stranded open-faced sandwich that mediates the dimer interface. Cofactor S-adenosyl-L-methionine (SAM) binds at the opening of the beta-barrel, and amino acids C-terminal to Lys27 in H3 and in the flexible C-terminal tail of the enzyme confer the specificity of this viral histone methyltransferase.
authors.affiliation: Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, One Gustave L. Levy Place, New York, New York 10029, USA.
authors.forename: Karishma L
authors.initials: KL
authors.lastname: Manzur
authors.forename: Amjad
authors.initials: A
authors.lastname: Farooq
authors.forename: Lei
authors.initials: L
authors.lastname: Zeng
authors.forename: Olga
authors.initials: O
authors.lastname: Plotnikova
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Koch
authors.lastname: Sachchidanand
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010247:Paramecium / Q000821:virology; D017862:Phycodnaviridae / Q000201:enzymology; D011487:Protein Conformation; D011496:Protein Methyltransferases; D017434:Protein Structure, Tertiary; D012436:S-Adenosylmethionine / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D014764:Viral Proteins; D012436:S-Adenosylmethionine; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine