9m0f | pdb_00009m0f

The crystal structure of BRD4-BDs in complex with H2A peptide

spinqualitylabelsall models 9m0f, resolution 2.61Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9m0f is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.61Å Ligands: ALY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease BRD4_HUMAN Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein. Function BRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). Publication Abstract from PubMed Bromodomain-containing protein 4 (BRD4) is well characterized as a histone acetyllysine reader that plays critical roles in the regulation of oncogene transcription. Additionally, BRD4 has been shown to be involved in DNA repair and telomere maintenance in a transcriptionally independent manner. Our previous study revealed that BRD4 inhibits non-homologous end-joining (NHEJ) DNA repair by recognizing the histone H2AK5acK9ac hyperacetylation at DSB sites through its tandem bromodomains (BD1 and BD2), resulting in the accumulation of the BRD4-KU80 protein that impedes the assembly of the DNA repair machinery in mitotic deacetylase complex (MiDAC)-deficient cells. Here we report the structural basis for the recognition of H2AK5acK9ac by BD1 and BD1-BD2 domains, respectively. In particular, we show that Leu92 in BD1 is a key determinant of the H2AK5acK9ac specificity over other diacetyllysine marks on H4, and it negatively regulates NHEJ repair to promote genomic instability in MiDAC-deficient cells. These results reveal a previously unrecognized mode of BRD4-histone interaction and its functional consequences that make a meaningful contribution to chromatin biology and DNA repair. Structural mechanism of diacetylated histone H2A recognition by Bromodomain-containing protein 4 in Regulation of non-homologous end-joining DNA repair.,Wang X, Ji J, Ma Y, Liu L, Bao K, Yang H, Li Z, Li T, Shi L, Yang N Int J Biol Macromol. 2026 Jun;368:152638. doi: 10.1016/j.ijbiomac.2026.152638. , Epub 2026 May 22. PMID:42173225 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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