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PDBsum entry 3jvk

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protein ligands links
Signaling protein PDB id
3jvk
Jmol PyMol
Contents
Protein chain
128 a.a. *
Ligands
GLY-GLY-ALY-ALA
EDO
Waters ×104
* Residue conservation analysis
PDB id:
3jvk
Name: Signaling protein
Title: Crystal structure of bromodomain 1 of mouse brd4 in complex with histone h3-k(ac)14
Structure: Bromodomain-containing protein 4. Chain: a. Fragment: bromodomain 1, unp residues 42-168. Synonym: mitotic chromosome-associated protein, mcap. Engineered: yes. Histone h3.3 peptide. Chain: c. Fragment: unp residues 13-20. Engineered: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Gene: brd4. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: fmoc solid phase synthesis
Resolution:
1.80Å     R-factor:   0.200     R-free:   0.259
Authors: F.Vollmuth,W.Blankenfeldt,M.Geyer
Key ref:
F.Vollmuth et al. (2009). Structures of the dual bromodomains of the P-TEFb activating protein Brd4 at atomic resolution. J Biol Chem, 284, 36547-36556. PubMed id: 19828451 DOI: 10.1074/jbc.M109.033712
Date:
17-Sep-09     Release date:   13-Oct-09    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9ESU6  (BRD4_MOUSE) -  Bromodomain-containing protein 4
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1400 a.a.
128 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 

 
DOI no: 10.1074/jbc.M109.033712 J Biol Chem 284:36547-36556 (2009)
PubMed id: 19828451  
 
 
Structures of the dual bromodomains of the P-TEFb activating protein Brd4 at atomic resolution.
F.Vollmuth, W.Blankenfeldt, M.Geyer.
 
  ABSTRACT  
 
Brd4 is a member of the bromodomains and extra terminal domain (BET) family proteins that recognize acetylated chromatin structures through their bromodomains and act as transcriptional activators. Brd4 functions as an associated factor and positive regulator of P-TEFb, a Cdk9-Cyclin T heterodimer that stimulates transcriptional elongation by RNA polymerase II. Here, the crystal structures of the two bromodomains of Brd4 (BD1 and BD2) were determined at 1.5 and 1.2 A resolution, respectively. Complex formation of BD1 with a histone H3 tail polypeptide encompassing residues 12-19 showed binding of the Nz-acetylated lysine 14 to the conserved asparagine 140 of Brd4. In contrast, in BD2 the N-terminal linker sequence was found to interact with the binding site for acetylated lysines of the adjacent molecule to form continuous strings in the crystal lattice. This assembly shows for the first time a different binding ligand than acetylated lysine indicating that also other sequence compositions may be able to form similar interaction networks. Isothermal titration calorimetry revealed best binding of BD1 to H3 and of BD2 to H4 acetylated lysine sequences, suggesting alternating histone recognition specificities. Intriguingly, an acetylated lysine motif from Cyclin T1 bound similarly well to BD2. While the structure of Brd2 BD1 suggested its dimer formation, both Brd4 bromodomains appeared monomeric in solution as shown by size exclusion chromatography and mutational analyses.
 
  Selected figure(s)  
 
Figure 3.
Electrostatic surface potential of the two Brd4 bromodomains. Displayed is the electrostatic surface potential from −15 k[B]T (red) to +15 k[B]T (blue) for BD1 (A) and BD2 (B). The binding site for acetylated lysines is indicated by arrows. Acidic residues on helices α[Z″] to α[A] and the BC loop form negatively charged surfaces surrounding the interaction cleft of both bromodomains (right panel).
Figure 5.
Structural basis of H3-K(ac)14 binding to Brd4 BD1. A, complex structure of the bromodomain 42–166 with the peptide GGK(ac)A from H3 (green). B, hydrogen bonds between the H3 peptide and the essential asparagine Asn-140 in BD1 define the interaction network. Several water molecules (colored red) in the binding cavity of the bromodomain surround the acetyl moiety.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 36547-36556) copyright 2009.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21157775 R.J.Falconer, and B.M.Collins (2011).
Survey of the year 2009: applications of isothermal titration calorimetry.
  J Mol Recognit, 24, 1.  
21068722 E.Nicodeme, K.L.Jeffrey, U.Schaefer, S.Beinke, S.Dewell, C.W.Chung, R.Chandwani, I.Marazzi, P.Wilson, H.Coste, J.White, J.Kirilovsky, C.M.Rice, J.M.Lora, R.K.Prinjha, K.Lee, and A.Tarakhovsky (2010).
Suppression of inflammation by a synthetic histone mimic.
  Nature, 468, 1119-1123.
PDB code: 3p5o
20923397 K.L.Yap, and M.M.Zhou (2010).
Keeping it in the family: diverse histone recognition by conserved structural folds.
  Crit Rev Biochem Mol Biol, 45, 488-505.  
20871596 P.Filippakopoulos, J.Qi, S.Picaud, Y.Shen, W.B.Smith, O.Fedorov, E.M.Morse, T.Keates, T.T.Hickman, I.Felletar, M.Philpott, S.Munro, M.R.McKeown, Y.Wang, A.L.Christie, N.West, M.J.Cameron, B.Schwartz, T.D.Heightman, N.La Thangue, C.A.French, O.Wiest, A.L.Kung, S.Knapp, and J.E.Bradner (2010).
Selective inhibition of BET bromodomains.
  Nature, 468, 1067-1073.
PDB codes: 3mxf 3oni
  20495683 C.M.Chiang (2009).
Brd4 engagement from chromatin targeting to transcriptional regulation: selective contact with acetylated histone H3 and H4.
  F1000 Biol Rep, 1, 98.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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