Acetylation of lysine

Kramer OH, Baus D, Knauer SK, Stein S, Jager E, Stauber RH, Grez M, Pfitzner E, Heinzel T (2006) Acetylation of Stall modulates NF-kappaB activity. Genes Dev 20(4) 473 85 Kumar BR, Swaminathan V, Banerjee S, Kundu TK (2001) p300-mediated acetylation of human transcriptional coactivator PC4 is inhibited by phosphorylation. J Biol Chem 276(20) 16804-16809 Lim JH, West KL, Rubinstein Y, Bergel M, Postnikov YV, Bustin M (2005) Chromosomal protein HMGNl enhances the acetylation of lysine 14 in histone H3. EMBO J 24(17) 3038-3048 Li M, Luo J, Brooks CL, Gu W (2002) Acetylation of p53 inhibits its ubiquitination by Mdm2. J Biol Chem 277(52) 50607-50611... 

A high proportion of the positiveiy charged basic amino acids lysine and arginine within these flexible tails are frequent targets for extensive posttranslational modifications (Berger, 2002). Such modifications include the acetylation of lysine residues, the methylation of lysine and arginine residues, the ubiquitination of lysine residues, the phosphorylation of serine and threonine residues, the sumoylation of lysine residues, and the poly ADP-ribosylation of glutamic acid residues. 

Scheme 13 N-acetylation of lysine. Lysine attacks the acetyl group of acetyl-CoA generating an acetylated protein and CoA.

The phenylselenocysteine has also been used successfully to chemically append analogues of methyl- or acetyl-lysine, important histone modifications that can contribute to chromatin structure and accessibility of transcriptional machinery in eukaryotes. By introducing phenylselenocysteine into the Xenopus histone H3, both acetyl-lysine and mono-, di-, and trimethyl-lysine analogues were appended to the purified unnatural amino acid-containing FI 3 protein (Figure 10). " Additionally, the H3 protein with a modification mimicking acetylation of lysine 9 can be deactylated by a histone deacetylation complex and is also a substrate for phosphorylation by Aurora B kinase. Such purified and chemically labeled histones are likely functional in nucleosomes, and preparation of specifically modified histones for comprehensive analysis of chromatin structure and accessibility is particularly suited to this chemical labeling technique. 

Acetylation is a reversible modification on proteins that can also contribute to protein localization and function. Acetylation of lysine residues in histone proteins can control the secondary structure of chromatin as well as gene expression levels from certain loci, and chromatin remodeling and its consequences in a variety of molecular and cell biological questions are intensely researched. Many other proteins undergo reversible acetylation, and the functional consequences of these modifications are poorly understood in many cases. 

A true appreciation of the subtle and complex ways in which the nucleosome can influence gene expression, has come only recently, largely through studies of the post-translational modifications to which all histones are subject and of the enzymes that add and remove these modifications. It has been known for many years that the histone N-terminal tails are exposed on the surface of the nucleosome and that selected amino acid residues are subject to a variety of enzyme-catalyzed, post-translational modifications. These include acetylation of lysines, phosphorylation of serines, and methylation of lysines and arginines ([6,7], see also chapters by Davie, and Ausio and Abbott, this volume). The locations of the histone N-terminal tails in the nucleosome and the residues that can be modified are shown in Fig. 1. 

Hackett, C.S., Novoa, W.B., Kensil, C.R. Strittmatter, P. (1988). NADH binding to cytochrome b5 reductase blocks the acetylation of lysine 110. Journal of Biological Chemistry 263, 7539—43. 

Figure 1 Histone modifications. The best-characterized human histone modifications are shown which include the acetylation of lysines (Ac), the methylation of lysines and arginines (Me)/ the phosphorylation of serine and threonines (Ph), and the ubiquitination of lysines (Ub). The vast majority of modifications are within the N-terminal domain of the histone tail/ but ubiquitination occurs at the C-terminal domain.

Protein phosphorylation is a pervasive posttranslational modification in cells. It is reversible and can dramatically affect the activity of a modified protein. Protein phosphorylation is one of the most important mechanisms used for signal transduction by cells. In prokaryotic cells, the best-known reversible protein phosphorylations occur on histidine and aspartate in eukaryotes the best-known occur on the hydroxyl groups of serine, threonine, and tyrosine, although histidine can also be phosphorylated (Fig. 3.9). Other reversible modifications also occur, such as the acetylation of lysine residues in histone proteins. 

The 43-unit mass difference between modified and unmodified peptides appeared because of acetylation of lysine along with deamidation of either asparagine (N) or glutamine (Q) residues present in... 

What effect might the acetylation of lysine residnes on a histone (Fig. 7-9) have on DNA packaging ... 

These studies with retinoids have provided some information about the structural requirements of the retinol binding site on RBP. No information is, however, available about the amino acid residues in RBP that are involved in the binding site. Acetylation of lysine residues of RBP did not affect its binding of retinol (Heller and Horwitz, 1975). Modification of one of eight tyrosine residues and two of four tryptophan residues of RBP also had no effect on the retinol-RBP interaction (Heller and Horwitz, 1975 Horwitz and Heller, 1974b). The binding site was, however, disrupted by reduction and alkylation of disulfide bonds (Raz et al., 1970). 

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