User:Benjamin Elliott/Crystal Structure of the Bromodomain-PHD Finger Module of Human Transcriptional Co-Activator CBP in complex with Acetylated Histone 4 Peptide (H4K20ac)

4N3W is a 2-domain complex of a bromodomain (BrD) and a plant homeodomain (PHD) that functions in humans to recognize the epigenetic acetylation of histones.

Function

Bromodomains (BrDs) function exclusively as acetyl-lysine binding domains to regulate gene transcription in both histone and non-histone proteins. This BrD of human transcriptional co-activator CBP binds with relatively high specificity to Lys20-acetylated histone H4 (H4K20), though this preference is not well-understood. The plant homeodomain (PHD) finger is hypothesized to play a structural role, since the entire module functions as one unit. It has been experimentally demonstrated that the module binds most effectively to singly acetylated peptide chains, with affinity significantly reduced with more acetylations. More specifically, it has been shown that the bromodomain prefers lysine-acetylated motifs comprising a hydrophobic or aromatic residue at -2 and a lysine or arginine at the -3 or -4 position^[1] . from the acetylated lysine.

Disease

Relevance

Bromodomains have become a popular target for their role in human disease since they recognize an epigenetic tag.

Structural highlights

This protein is composed of two different domains -- the bromodomain (BrD) and the plant homeodomain (PHD) finger. In this particular module for human CBP, the two come together to form such interactions that they function as a single structural unit.There are two that serve as a stable base for an extended interface established between the PHD finger and the BrD. The PHD finger itself has not shown to bind any specific peptide, whether in tandem or in its individual construct. The separation of the domains is shown , with the BrD shown in aquamarine, the PHD finger shown in red, and the linkers of the two domains shown in blue.

There are two different sections which are missing electron density in their region, which suggests a high degree of structural mobility in solution. These regions are from and . Though unshown in the crystal structure,

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