Solution structure of BRD7 bromodomain and its interaction with acetylated peptides from histone H3 and H4.
BRD7 is an important protein tightly associated with Nasopharyngeal carcinoma (NPC). Overexpression of BRD7 inhibits NPC cell growth and cell cycle by transcriptionally regulating the cell cycle related genes. BRD7 contains a bromodomain that is found in many chromatin-associated proteins and in nearly all known nuclear histone acetyltransferases (HATs) and plays an important role in chromatin remodeling and transcriptional activation. Here, we report the solution structure of BRD7 bromodomain determined by NMR spectroscopy, and its binding specificity revealed by NMR titration with several acetylated histone peptides. We find that BRD7 bromodomain contains the typical left-handed four-helix bundle topology, and can bind with weak affinity to lysine-acetylated peptides derived from histone H3 with K9 or K14 acetylated and from histone H4 with K8, K12 or K16 acetylated. Our results show that BRD7 bromodomain lacks inherent binding specificity when binding to histones in vitro.
Sun
Hongbin
H
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China.
Liu
Jiangxin
J
Zhang
Jiahai
J
Shen
Weiqun
W
Huang
Hongda
H
Xu
Chao
C
Dai
Haiming
H
Wu
Jihui
J
Shi
Yunyu
Y
D000107:Acetylation; D000595:Amino Acid Sequence; D001665:Binding Sites; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000648:ultrastructure*; D003198:Computer Simulation; D006657:Histones / Q000737:chemistry* / Q000648:ultrastructure; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D000092468:Bromodomain Containing Proteins
D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009687:Nuclear Proteins; D010455:Peptides; C485694:BRD7 protein, human; D000092468:Bromodomain Containing Proteins