Acetyl lysine-binding domain

Zeng L, Zhou MM (2002) Bromodomain an acetyl-lysine binding domain. EEBS letters 513 124-128 Zhang Y, Reinberg D (2001) Transcription regulation by histone methylation interplay between different covalent modifications of the core histone tails. Genes Dev 15 2343-2360... 

The co-repressor KAP-1 functionally links the DNA-binding Kruppel-associated box zinc finger proteins to the NURD complex by recruiting the Mi-2a subunit. [251]. This interaction requires a tandem PHD/bromodomain motif in which the individual domains appear to act together as a functional unit. The nature of any possible acetylated lysine targets of the bromodomain remains unclear but it is not excluded that this domain could bind to an acetylated lysine in Mi-2a rather than to an acetylated histone tail. 

In addition, the acetylated lysine residues interact with a specific acetyilysine-binding domain that is present in many proteins that regulate eukaryotic transcription. This domain, termed a bromodomain, comprises approximately 110 amino acids that form a four-helix bundle containing a peptide-binding site at one end (Figure 31.31). 

New evidence indicates that the major mediators in remodeler recruitment may be bromo and chromo domain-containing proteins. Bromo domains mediate protein binding to acetyl-lysines in histones and other proteins (Jacobson et al., 2000), and chromo domains have been shown to bind methyl-lysines (Jacobs et al., 2002). For instance, TAF1, a component of TFIID, contains two tandem bromo domains that bind selectively to multiply acetylated H4 peptides (Jacobson et al., 2000). Furthermore, the Gcn5 bromo domain preferentially binds acetylated H4 K16 (Owen et al., 2000). 

Fig. 2. Acetyl-CoA carboxylase. (A) Eukaryotic ACCs contain -2300 residues organized into three functional domains — biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT). The role of the region between the biotin carboxyl carrier and carboxyltransferase domains is unknown. The biotin carboxyl carrier protein contains a typical conserved biotin attachment-site motif, VMKMV. The sites of phosphorylation are indicated by asterisks. (B) Electron micrograph of polymerized rat acetyl-CoA carboxylase (F. Ahmad, 1978). (C) Crystal structure of the biotin carboxylase domain of the yeast enzyme. In the presence of soraphen A, the biotin carboxyl carrier protein domain forms an inactive monomer the likely position of the modeled ATP-binding site is shown (adapted from Ref. [2]). (D) Crystal structure of the dimeric carboxyltransferase domain of the yeast enzyme. Although acetyl-CoA was included in the crystallization, density was observed only for CoA at one site and adenine at the other (adapted from Ref. [2]). (E) NMR structure of the biotin carboxyl carrier apoprotein domain of the human ACC2 The lysine attachment site for biotin is shown (RIKEN Structural Genomics/Proteomics Initiative, 2006). (See color plate section, plate no. 3.)...

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