3jvj | pdb_00003jvj

Crystal structure of the bromodomain 1 in mouse Brd4

spinqualitylabelsall models 3jvj, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3jvj is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, GOL Gene: Brd4 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [BRD4_MOUSE] Plays a role in a process governing chromosomal dynamics during mitosis. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Brd4 is a member of the bromodomains and extra terminal domain (BET) family of 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 Nzeta-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. Whereas 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. Structures of the dual bromodomains of the P-TEFb-activating protein Brd4 at atomic resolution.,Vollmuth F, Blankenfeldt W, Geyer M J Biol Chem. 2009 Dec 25;284(52):36547-56. Epub 2009 Oct 13. PMID:19828451 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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