Solution structure of the extraterminal domain of the bromodomain-containing protein BRD4.
BRD4, which is a member of the BET (bromodomains and extraterminal) protein family, interacts preferentially with acetylated chromatin and possesses multiple cellular functions in meiosis, embryonic development, the cell cycle, and transcription. BRD4 and its family members contain two bromodomains known to bind acetylated lysine, and a conserved ET domain whose function is unclear. Here we show the solution structure of the ET domain of mouse BRD4, which provides the first three-dimensional structure of an ET domain in the BET family. We determined the NMR structure of BRD4-ET with a root-mean-square deviation of 0.41 A for the backbone atoms in the structured region of residues 608-676 on the basis of 1793 upper distance limits derived from NOE intensities measured in three-dimensional NOESY spectra. The structure of the BRD4-ET domain comprises three alpha-helices and a characteristic loop region of an irregular but well-defined structure. A DALI search revealed no close structural homologs in the current Protein Data Bank. The BRD4-ET structure has an acidic patch that forms a continuous ridge with a hydrophobic cleft, which may interact with other proteins and/or DNA.
Lin
Yi-Jan
YJ
1Tatsuo Miyazawa Memorial Program, RIKEN Genomic Sciences Center, Yokohama 230-0045, Japan.
Umehara
Takashi
T
Inoue
Makoto
M
Saito
Kohei
K
Kigawa
Takanori
T
Jang
Moon-Kyoo
MK
Ozato
Keiko
K
Yokoyama
Shigeyuki
S
Padmanabhan
Balasundaram
B
Güntert
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D030562:Databases, Protein; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D000092468:Bromodomain Containing Proteins
D009687:Nuclear Proteins; D014157:Transcription Factors; C486694:Brd4 protein, mouse; D000092468:Bromodomain Containing Proteins