The structural basis for the recognition of acetylated histone H4 by the bromodomain of histone acetyltransferase Gcn5p

The bromodomain is an similar to 110 amino acid module found in histone ace tyltransferases and the ATPase component of certain nucleosome remodelling complexes. We report the crystal structure at 1.9 Angstrom resolution of th e Saccharomyces cerevisiae Gcn5p bromodomain complexed with a peptide corre sponding to residues 15-29 of histone H4 acetylated at the zeta -N of lysin e 16. We show that this bromodomain preferentially binds to peptides contai ning an N-acetyl lysine residue. Only residues 16-19 of the acetylated pept ide 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 acet yl carbonyl group. A network of water-mediated H-bonds with protein main ch ain carbonyl groups at the base of the cleft contributes to the binding. Ad ditional side chain binding occurs on a shallow depression that is hydropho bic at one end and can accommodate charge interactions at the other. These findings suggest that the Gcn5p bromodomain may discriminate between differ ent acetylated lysine residues depending on the context in which they are d isplayed.