7to7

BRD3-BD1 in complex with RaPID linear peptide 1xAcK.4XE (monoAcK.4xE)

spinqualitylabelsall models 7to7, resolution 1.93Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7to7 is a 6 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.93Å Ligands: ALY, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease BRD3_HUMAN Note=A chromosomal aberration involving BRD3 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;9)(q14;q34) with NUT which produces a BRD3-NUT fusion protein. Function BRD3_HUMAN Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling and interaction with transcription factors. Regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (By similarity). Regulates transcription of the CCND1 gene. Publication Abstract from PubMed Bromodomains (BDs) regulate gene expression by recognizing protein motifs containing acetyllysine. Although originally characterized as histone-binding proteins, it has since become clear that these domains interact with other acetylated proteins, perhaps most prominently transcription factors. The likely transient nature and low stoichiometry of such modifications, however, has made it challenging to fully define the interactome of any given BD. To begin to address this knowledge gap in an unbiased manner, we carried out mRNA display screens against a BD-the N-terminal BD of BRD3-using peptide libraries that contained either one or two acetyllysine residues. We discovered peptides with very strong consensus sequences and with affinities that are significantly higher than typical BD-peptide interactions. X-ray crystal structures also revealed modes of binding that have not been seen with natural ligands. Intriguingly, however, our sequences are not found in the human proteome, perhaps suggesting that strong binders to BDs might have been selected against during evolution. mRNA display reveals a class of high-affinity bromodomain-binding motifs that are not found in the human proteome.,Low JKK, Patel K, Jones N, Solomon P, Norman A, Maxwell JWC, Pachl P, Matthews JM, Payne RJ, Passioura T, Suga H, Walport LJ, Mackay JP J Biol Chem. 2023 Dec;299(12):105482. doi: 10.1016/j.jbc.2023.105482. Epub 2023 , Nov 20. PMID:37992806 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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