The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase Gcn5p
AUTOR(ES)
Owen, David J.
FONTE
Oxford University Press
RESUMO
The bromodomain is an ∼110 amino acid module found in histone acetyltransferases and the ATPase component of certain nucleosome remodelling complexes. We report the crystal structure at 1.9 Å resolution of the Saccharomyces cerevisiae Gcn5p bromodomain complexed with a peptide corresponding to residues 15–29 of histone H4 acetylated at the ζ-N of lysine 16. We show that this bromodomain preferentially binds to peptides containing an N-acetyl lysine residue. Only residues 16–19 of the acetylated peptide interact with the bromodomain. The primary interaction is the N-acetyl lysine binding in a cleft with the specificity provided by the interaction of the amide nitrogen of a conserved asparagine with the oxygen of the acetyl carbonyl group. A network of water-mediated H-bonds with protein main chain carbonyl groups at the base of the cleft contributes to the binding. Additional side chain binding occurs on a shallow depression that is hydrophobic at one end and can accommodate charge interactions at the other. These findings suggest that the Gcn5p bromodomain may discriminate between different acetylated lysine residues depending on the context in which they are displayed.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=305837Documentos Relacionados
- Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo
- The histone H4 acetyltransferase MOF uses a C2HC zinc finger for substrate recognition
- Characterization of yeast histone H3-specific type B histone acetyltransferases identifies an ADA2-independent Gcn5p activity
- Acetylated histone H4 is preferentially associated with template-active chromatin.
- Repression of GCN5 Histone Acetyltransferase Activity via Bromodomain-Mediated Binding and Phosphorylation by the Ku–DNA-Dependent Protein Kinase Complex