9M0F
The crystal structure of BRD4-BDs in complex with H2A peptide
Summary for 9M0F
| Entry DOI | 10.2210/pdb9m0f/pdb |
| Related | 9KEM |
| Descriptor | Bromodomain-containing protein 4, Histone H2A, ... (4 entities in total) |
| Functional Keywords | bromodomain, acetylation, protein binding |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 54693.32 |
| Authors | Wang, X.D.,Ji, J.H.,Yang, H.W.,Li, Z.B.,Yang, N. (deposition date: 2025-02-24, release date: 2026-07-01) |
| Primary citation | Wang, X.,Ji, J.,Ma, Y.,Liu, L.,Bao, K.,Yang, H.,Li, Z.,Li, T.,Shi, L.,Yang, N. Structural mechanism of diacetylated histone H2A recognition by Bromodomain-containing protein 4 in Regulation of non-homologous end-joining DNA repair. Int.J.Biol.Macromol., 368:152638-152638, 2026 Cited by PubMed Abstract: 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. PubMed: 42173225DOI: 10.1016/j.ijbiomac.2026.152638 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.61 Å) |
Structure validation
No wwPDB Validation report is currently available for this entry.
