Structural ramification for acetyl-lysine recognition by the bromodomain of human BRG1 protein, a central ATPase of the SWI/SNF remodeling complex

Bromodomains represent an extensive family of evolutionarily conserved domains that are found in many chromatin-associated proteins such as histone acetyltransferases (HAT) and subunits of ATP-dependent chromatin-remodeling complexes. These domains are associated with acetylated lysine residues that bind both in vivo and in vitro; for example, they bind to the N-acetylated lysines of the histone tail of nucleosomes. In this report, we determined the structure of the bromodomain from human brahmorelated gene 1 (BRG1) protein, a subunit of an ATP-dependent switching/sucrose nonfermenting (SWI/SNF) remodeling complex, and have also characterized its in vitro interaction with N-acetylated lysine peptides from histones. In addition to a typical all-alpha-helical fold that was observed in the bromodomains, we observed for the first time a small P-sheet in the ZA loop region of the BRG1 protein. The BRG1 bromodomain exhibited binding, albeit weak, to acetylated peptides that were derived from histones H3 and H4. We have compared the acetyl-lysine binding sites of BRG1 bromodomain with the yGCN5 (general control of amino acid biosynthesis). By modeling the acetylated-lysine peptide into the BRG1 bromodomain structure, we were able to explain the weak binding of acetylated-lysine peptides to this bromodomain.