Post-translational modifications proteomics

Combining ID and IF -> 2D protein gels —> detect post-translational modification proteomics tool... 

Fagerquist, C.K., Bates,A.H.,Heath,S.,King,B.C., Garbus, B.R., Harden, L.A., Miller, W.G. (2006) Sub-speciating Campylobacter jejuni by proteomic analysis of its protein biomarkers and their post-translational modifications. /. Proteome Res.,5, 2527-2538. 

Proteomics, the measurement of the global changes in proteins produced as a result of gene expression, bridges the gap between genome sequence and cellular behaviour and takes into account the post-translational modifications that often result in the functional effect. It has the potential to determine the role of protein-protein complexes in the complex signalling cascades that... 

Post-translational modification of proteins plays a critical role in cellular function. For, example protein phosphorylation events control the majority of the signal transduction pathways in eukaryotic cells. Therefore, an important goal of proteomics is the identification of post-translational modifications. Proteins can undergo a wide range of post-translational modifications such as phosphorylation, glycosylation, sulphonation, palmitoylation and ADP-ribosylation. These modifications can play an essential role in the function of the protein and mass spectrometry has been used to characterize such modifications. 

Demirev, P. A. Lin, J. S. Pineda, F. J. Fenselau, C. Bioinformatics and mass spectrometry for microorganism identification Proteome-wide post-translational modifications and database search algorithms for characterization of intact H. Pylori. Anal. Chem. 2001, 73, 4566 573. 

Farriol-Mathis, N., Garavelli, J.S., Boeckmann, B., Duvaud, S., Gasteiger, S.E., Gateau, E., Veuthey, A.-L., Bairoch, A. (2004). Annotation of post-translational modifications in the Swiss-Prot knowledge base. Proteomics 4, 1537. 

Mann, M., Jensen, O.L. (2003). Proteomic analysis of post-translational modifications. Nature Biotech. 21, 255. 

Jensen, O.N. (2004). Modification-specific proteomics characterization of post-translational modifications by mass spectrometry. Curr. Opin. Chem. Biol. 8, 33 11. 

Kim, J. K., Mastronardi, F. G., Wood, D. D. etal. Multiple sclerosis an important role for post-translational modifications of myelin basic protein in pathogenesis. Mol. Cell. Proteomics 2 453-462, 2003. 

Compared to the genome, the proteome (the entire diverse protein content of a cell) is a far more dynamic system. Proteins imdergo post-translational modifications such as phosphorylation, glycosylation and sulphation, as well as cleavage for specific proteins. These alterations determine protein activity, localisation and turnover. All are subject to change following a toxic insult and, in some ways, the study of proteins holds more promise than the study of gene expression as the former is nearer to key activities in the cell. 

Unlike the genome the proteome is not a static but a dynamic and constantly changing entity that is cell- and tissue-specific and dependent on the environment. Because of the dynamic nature of protein expression and fimction, these properties need to be determined quantitatively in a time-dependent manner. Proteomics, the study of the proteome, involves the analysis of the complete pattern of the expressed proteins and their post-translational modifications in a cell, tissue, or body fluid. An integrated view of any living system hence requires an analysis that takes into account the spatial as well as temporal distribution of all the proteins in a cell or tissue. The analytical effort that is necessary to deliver such an integrated view is by several orders of magnitude more complicated than that of the recently finished human genome (Lander ef al. 2001 Venter et al. 2001). 

Fig.1 From genome to transcriptome to proteome. Through alternate splicing a single gene can be transcribed into several mRNAs. Every mRNA that is subsequently translated can give rise to more than one protein caused by differential post-translational modifications as indicated hypurple symbols...

Proteomics includes a variety of technologies that include differential protein display on gels, protein chips, quantitation of protein amoimts, analysis of post-translational modifications, characterization of protein complexes and networks and bioinformatics. All this information in combination with genome and phenotype studies will ultimately yield a comprehensive picture of a cellular or tissue proteome (Wasinger and Corthals 2002). 

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