Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase.
AdoMet-dependent methylation of histones is part of the "histone code" that can profoundly influence gene expression. We describe the crystal structure of Neurospora DIM-5, a histone H3 lysine 9 methyltranferase (HKMT), determined at 1.98 A resolution, as well as results of biochemical characterization and site-directed mutagenesis of key residues. This SET domain protein bears no structural similarity to previously characterized AdoMet-dependent methyltransferases but includes notable features such as a triangular Zn3Cys9 zinc cluster in the pre-SET domain and a AdoMet binding site in the SET domain essential for methyl transfer. The structure suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the HKMT family and the SET domain.
Zhang
Xing
X
Department of Biochemistry, School of Medicine, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA.
Tamaru
Hisashi
H
Khan
Seema I
SI
Horton
John R
JR
Keefe
Lisa J
LJ
Selker
Eric U
EU
Cheng
Xiaodong
X
D000595:Amino Acid Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000737:chemistry*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009491:Neurospora / Q000201:enzymology*; D009687:Nuclear Proteins / Q000737:chemistry*; D063151:Polycomb Repressive Complex 2; D011485:Protein Binding; D011496:Protein Methyltransferases; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D012097:Repressor Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D014157:Transcription Factors; D014466:Ultraviolet Rays; D014961:X-Ray Diffraction; D015032:Zinc / Q000737:chemistry
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C063460:Trl protein, Drosophila; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; C083329:E(z) protein, Drosophila; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D015032:Zinc