ABSTRACT
Proteomics is the global analysis of the protein species derived from a genome (the proteome). Proteins are made up of 20 amino acids, each encoded for by three nucleotides. Similar to genomics, proteomics utilizes the unique sequence of amino acids in each protein to identify them. Unlike genomics, where the relative complexity of the analysis is determined by the presence of alternative gene forms, proteomics must deal with virtually limitless differences in protein chemistry and potential modifications. Therefore, the complexity of proteomics is generally underappreciated by the casual observer. A typical gene for instance may have multiple different isoforms, which can be generated by alternative splicing of the transcript, generating two different proteins. Now consider the potential magnification in complexity of these proteins (Fig. 38.1). During translation through the secretory pathway for instance, there may be different degrees of folding in the endoplasmic reticulum. Although folding is not a post-translational modification (PTM), it can affect whether the potential sites for the addition of PTMs are available. Upon proper folding, the protein is now able to travel through the Golgi body, where it can be glycoslyated. Since there can be different degrees of glcyosylation, each one of these now qualifies as a new protein (for the sake of
proteomics), since each of these species may have a unique function or give a unique representation of a disease. Further export of a protein can reveal the cytoplasmic tail of the protein, which can now be acylated, ubiquinated or phosphorylated, or a combination of all (or some) of the above, in addition to many other PTMs. Considering only three potential differences at each of these steps, we now have at least 2(3n) unique proteins where n represents the number of steps. Following translation, each different form of the protein can be modified by as many as 500 known PTMs,1 producing a staggering array of protein products. PTMs are modifications to proteins by the addition of a modifying group to one or more amino acids (Table 38.1), or proteolytic cleavage which can affect protein activity, interactions, and cellular localization. Translocation of proteins to specific subcellular regions allows the same proteins to exert different biological effects or act as an alternative form of protein control, often resulting in an observable cellular phenotype. In contrast to the genome, which is a static blueprint, the proteome is a dynamic system of production, modification and degradation. It is the dynamic nature of the proteome which determines the phenotype of the cell. The changes in the proteome also characterize the cell’s response to change in the environment that induces disease. Thus, the characterization of a cell’s proteome allows one to understand the disease processes.
