5NNF
Crystal Structure of the first bromodomain of human BRD4 in complex with an acetylated BAZ1B peptide (K221ac)
Summary for 5NNF
Entry DOI | 10.2210/pdb5nnf/pdb |
Descriptor | Bromodomain-containing protein 4, FLPH(ALY)YDVKL (3 entities in total) |
Functional Keywords | bromodomain, transcription, complex |
Biological source | Homo sapiens (Human) More |
Total number of polymer chains | 2 |
Total formula weight | 16402.93 |
Authors | Filippakopoulos, P.,Picaud, S.,Krojer, T.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C. (deposition date: 2017-04-08, release date: 2018-05-16, Last modification date: 2024-10-16) |
Primary citation | Lambert, J.P.,Picaud, S.,Fujisawa, T.,Hou, H.,Savitsky, P.,Uuskula-Reimand, L.,Gupta, G.D.,Abdouni, H.,Lin, Z.Y.,Tucholska, M.,Knight, J.D.R.,Gonzalez-Badillo, B.,St-Denis, N.,Newman, J.A.,Stucki, M.,Pelletier, L.,Bandeira, N.,Wilson, M.D.,Filippakopoulos, P.,Gingras, A.C. Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. Mol. Cell, 73:621-638.e17, 2019 Cited by PubMed Abstract: Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions. Last, we identify an unexpected increase in several interactions following JQ1 treatment that define negative functions for BRD3 in the regulation of rRNA synthesis and potentially RNAPII-dependent gene expression that result in decreased cell proliferation. Together, our data highlight the contributions of BET protein modules to their interactomes allowing for a better understanding of pharmacological rewiring in response to JQ1. PubMed: 30554943DOI: 10.1016/j.molcel.2018.11.006 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.15 Å) |
Structure validation
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