Structure and Ligand of a Histone Acetyltransferase Bromodomain

Nature. 1999 Jun 3;399(6735):491-6. doi: 10.1038/20974.

Abstract

Histone acetylation is important in chromatin remodelling and gene activation. Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are approximately 110-amino-acid modules found in many chromatin-associated proteins. Despite the wide occurrence of these bromodomains, their three-dimensional structure and binding partners remain unknown. Here we report the solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor). The structure reveals an unusual left-handed up-and-down four-helix bundle. In addition, we show by a combination of structural and site-directed mutagenesis studies that bromodomains can interact specifically with acetylated lysine, making them the first known protein modules to do so. The nature of the recognition of acetyl-lysine by the P/CAF bromodomain is similar to that of acetyl-CoA by histone acetyltransferase. Thus, the bromodomain is functionally linked to the HAT activity of co-activators in the regulation of gene transcription.

Publication types

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

MeSH terms

  • Acetyltransferases / chemistry
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Amino Acid Sequence
  • Bromine Compounds / chemistry
  • Bromine Compounds / metabolism*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • Crystallography, X-Ray
  • Escherichia coli
  • Histone Acetyltransferases
  • Ligands
  • Lysine / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Transcription Factors
  • p300-CBP Transcription Factors

Substances

  • Bromine Compounds
  • Cell Cycle Proteins
  • Ligands
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Lysine

Associated data

  • PDB/1B91