Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase

Cell. 2002 Oct 4;111(1):117-27. doi: 10.1016/s0092-8674(02)00999-6.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • DNA-Binding Proteins / chemistry*
  • Dose-Response Relationship, Drug
  • Drosophila Proteins / chemistry*
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase*
  • Histones / metabolism*
  • Hydrogen-Ion Concentration
  • Methyltransferases / chemistry*
  • Methyltransferases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Neurospora / enzymology*
  • Nuclear Proteins / chemistry*
  • Polycomb Repressive Complex 2
  • Protein Binding
  • Protein Methyltransferases
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Repressor Proteins / chemistry*
  • Sequence Homology, Amino Acid
  • Temperature
  • Transcription Factors*
  • Ultraviolet Rays
  • X-Ray Diffraction
  • Zinc / chemistry

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Histones
  • Nuclear Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • Transcription Factors
  • Trl protein, Drosophila
  • Histone Methyltransferases
  • Methyltransferases
  • Protein Methyltransferases
  • E(z) protein, Drosophila
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2
  • Zinc