About BRD / Bromodomain Containing:
A bromodomain, or BRD, is an amino acid protein domain that is capable of recognizing acetylated lysine residues and regulating gene expression. By reading these lysine residues, BRD carriy and translate the signal released by acetylated lysine residues into phenotypes.
BRD-containing proteins have multiple and varied functions. Bromodomain and extra-terminal domain (BET) is perhaps, the most well-known example of a BRD containing protein, although ASH1L also contains bromodomain.
Bromodomain Containing Mechanism
BRD proteins read acetylation marks on histones and convert the signal released into observable characteristics, or phenotypes. The presence of BRD is often necessary for chromatin remodeling and a protein-histone association to occur. Studies have shown that BRD translates deregulated cell acetylome into phenotypes associated with diseases, including cancer and multiple sclerosis (MS). Additionally, BRD-containing proteins have been found in oncogenic fusion proteins, which result from chromosomal rearrangements.
Bromodomain containing proteins have been shown to interact with a variety of materials, including ATAD2, BAZ2B, BPTF, BRD2, BRD3, BRD4, BRDT, BRD7, CECR2, CREBBP, EP300, GCN5, KIAA1240, all 6 single domains of PB1, PCAF, SMARCA2, SMARCA4, TAF1, TIF1a (PHD/BRD), TRIM33A (PHD/BRD).
Due to the role of BRD in human diseases, BRD inhibitors are now being used in clinical trials to determine whether they can be used to effectively treat cancers.
Bromodomain Containing Structure
BRD presents as an all-α protein fold and features a bundle of four alpha helices. Each of these alpha helices are separated by loop regions. These loop regions are present in varying lengths and form a hydrophobic pocket, which facilitates the recognition of acetyl-lysine.