Abstract
Several studies have contributed to our knowledge of the enzymology underlying acetylation, including focused efforts to understand the molecular mechanism of substrate recognition by several acetyltransferases; however, conventional experiments to determine intrinsic features of substrate site specificity have proven challenging. In this chapter, I describe in detail a computational method that involves clustering analysis of protein sequences to predict protein acetylation based on the sequence characteristics of acetylated lysines within histones. This method illustrates that sequence composition has predictive power on datasets of acetylation marks, and can be used to predict other posttranslational modifications such as methylation and phosphorylation. Later in this chapter, other recent methods to predict lysine acetylation are described and together, these approaches combined with more traditional experimental methods, can be useful for identifying acetylated substrates proteome-wide.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Mujtaba S, Zeng L, Zhou MM (2007) Structure and acetyl-lysine recognition of the bromodomain. Oncogene 26:5521–5527
Liu X, Wang L, Zhao K, Thompson PR, Hwang Y, Marmorstein R et al (2008) The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature 451:846–850
Marmorstein R (2001) Structure of histone acetyltransferases. J Mol Biol 311:433–444
Marmorstein R, Roth SY (2001) Histone acetyltransferases: function, structure, and catalysis. Curr Opin Genet Dev 11:155–161
Wang L, Tang Y, Cole PA, Marmorstein R (2008) Structure and chemistry of the p300/CBP and Rtt109 histone acetyltransferases: implications for histone acetyltransferase evolution and function. Curr Opin Struct Biol 18: 741–747
Rojas JR, Trievel RC, Zhou J, Mo Y, Li X, Berger SL et al (1999) Structure of Tetrahymena GCN5 bound to coenzyme A and a histone H3 peptide. Nature 401:93–98
Glozak MA, Sengupta N, Zhang X, Seto E (2005) Acetylation and deacetylation of non-histone proteins. Gene 363:15–23
Sterner DE, Berger SL (2000) Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64:435–459
Yang XJ, Seto E (2008) Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 31:449–461
Gu W, Roeder RG (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90:595–606
Cereseto A, Manganaro L, Gutierrez MI, Terreni M, Fittipaldi A, Lusic M et al (2005) Acetylation of HIV-1 integrase by p300 regulates viral integration. EMBO J 24:3070–3081
Wynshaw-Boris A (2009) Elongator bridges tubulin acetylation and neuronal migration. Cell 136:393–394
Ozaki T, Okoshi R, Sang M, Kubo N, Nakagawara A (2009) Acetylation status of E2F-1 has an important role in the regulation of E2F-1-mediated transactivation of tumor suppressor p73. Biochem Biophys Res Commun 386:207–211
Kim SC, Sprung R, Chen Y, Xu Y, Ball H, Pei J et al (2006) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23:607–618
Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC et al (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325:834–840
Kimura A, Horikoshi M (1998) How do histone acetyltransferases select lysine residues in core histones? FEBS Lett 431:131–133
Kimura A, Horikoshi M (1998) Tip60 acetylates six lysines of a specific class in core histones in vitro. Genes Cells 3:789–800
Bannister AJ, Miska EA, Gorlich D, Kouzarides T (2000) Acetylation of importin-alpha nuclear import factors by CBP/p300. Curr Biol 10: 467–470
Hirayama J, Sahar S, Grimaldi B, Tamaru T, Takamatsu K, Nakahata Y et al (2007) CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature 450: 1086–1090
Sampath SC, Marazzi I, Yap KL, Krutchinsky AN, Mecklenbrauker I, Viale A et al (2007) Methylation of a histone mimic within the histone methyltransferase G9a regulates protein complex assembly. Mol Cell 27:596–608
Marmorstein R (2001) Structure and function of histone acetyltransferases. Cell Mol Life Sci 58:693–703
Eddy SR (2004) Where did the BLOSUM62 alignment score matrix come from? Nat Biotechnol 22:1035–1036
Cooper GF, Aliferis CF, Ambrosino R, Aronis J, Buchanan BG, Caruana R et al (1997) An evaluation of machine-learning methods for predicting pneumonia mortality. Artif Intell Med 9:107–138
Schwartz D, Chou MF, Church GM (2009) Predicting protein post-translational modifications using meta-analysis of proteome scale data sets. Mol Cell Proteomics 8: 365–379
Gnad F, Ren S, Choudhary C, Cox J, Mann M (2010) Predicting post-translational lysine acetylation using support vector machines. Bioinformatics 26:1666–1668
Gnad F, de Godoy LM, Cox J, Neuhauser N, Ren S, Olsen JV et al (2009) High-accuracy identification and bioinformatic analysis of in vivo protein phosphorylation sites in yeast. Proteomics 9:4642–4652
Gnad F, Ren S, Cox J, Olsen JV, Macek B, Oroshi M et al (2007) PHOSIDA (phosphorylation site database): management, structural and evolutionary investigation, and prediction of phosphosites. Genome Biol 8:R250
Chang WC, Lee TY, Shien DM, Hsu JB, Horng JT, Hsu PC et al (2009) Incorporating support vector machine for identifying protein tyrosine sulfation sites. J Comput Chem 30: 2526–2537
Li A, Xue Y, Jin C, Wang M, Yao X (2006) Prediction of Nepsilon-acetylation on internal lysines implemented in Bayesian Discriminant Method. Biochem Biophys Res Commun 350:818–824
Xu Y, Wang XB, Ding J, Wu LY, Deng NY (2010) Lysine acetylation sites prediction using an ensemble of support vector machine classifiers. J Theor Biol 264:130–135
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Basu, A. (2013). Computational Prediction of Lysine Acetylation Proteome-Wide. In: Hake, S., Janzen, C. (eds) Protein Acetylation. Methods in Molecular Biology, vol 981. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-305-3_10
Download citation
DOI: https://doi.org/10.1007/978-1-62703-305-3_10
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-304-6
Online ISBN: 978-1-62703-305-3
eBook Packages: Springer Protocols