Mujtaba S, Zeng L, Zhou M-M
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Oncogene. 2007 Aug 13;26(37):5521-7. doi: 10.1038/sj.onc.1210618.
Histone lysine acetylation is central to epigenetic control of gene transcription. The bromodomain, found in chromatin-associated proteins and histone acetyltranferases, functions as the sole protein module known to bind acetyl-lysine motifs. Recent structural and functional analyses of bromodomains' recognition of lysine-acetylated peptides derived from major acetylation sites in histones and cellular proteins provide new insights into differences in ligand binding selectivity as well as unifying features of histone recognition by the bromodomains. These new findings highlight the functional importance of bromodomain/acetyl-lysine binding as a pivotal mechanism for regulating protein-protein interactions in histone-directed chromatin remodeling and gene transcription. These new studies also support the notion that functional diversity of a conserved bromodomain structural fold is achieved by evolutionary changes of structurally flexible amino-acid sequences in the ligand binding site such as the ZA and BC loops.
组蛋白赖氨酸乙酰化对于基因转录的表观遗传控制至关重要。存在于染色质相关蛋白和组蛋白乙酰转移酶中的溴结构域，是已知唯一能结合乙酰赖氨酸基序的蛋白质模块。最近对溴结构域识别来自组蛋白和细胞蛋白主要乙酰化位点的赖氨酸乙酰化肽的结构和功能分析，为配体结合选择性的差异以及溴结构域识别组蛋白的统一特征提供了新见解。这些新发现突出了溴结构域/乙酰赖氨酸结合作为调节组蛋白导向的染色质重塑和基因转录中蛋白质-蛋白质相互作用的关键机制的功能重要性。这些新研究还支持这样一种观点，即保守的溴结构域结构折叠的功能多样性是通过配体结合位点（如ZA和BC环）中结构灵活的氨基酸序列的进化变化实现的。
