Proteome & Proteomics
"Proteins are central to our understanding of cellular function and disease processes, and without a concerted effort in proteomics, the fruits of genomics will go unrealized." Nature 409, 747 (2001)
Now that the human genome has been sequenced, we face the greater challenge of making use of this information for improving healthcare and discovering new drugs. There is an increasing interest in proteomics technologies now because DNA sequence information provides only a static snapshot of the various ways in which the cell might use its proteins whereas the life of the cell is a dynamic process. With this background, DNA/RNA (ribonucleic acid) sequences, per se, are not enough for the clear identification of a therapeutic target because proteins and not DNA/RNA are the basis of mode of action of drugs. Structural genomics is the determination of structure of proteins, RNA and other biological macromolecules. Functional genomics is an ambitious attempt at high-throughput basic research through the integration of multiple automated technologies including RNA profiling, proteomics, genetics of animal models, assays, structural biology and bioinformatics. Parallel to these developments, there is an interest in functional proteomics - study of function of proteins
What is proteome & proteomics?
‘PROTEOME is the PROTEINS expressed by a genome or a tissue’ (Wasinger et al. 1995)
The proteome has been defined as the entire complement of proteins expressed by a cell, organism, or tissue type, and accordingly, proteomics is the study of this complement expressed at a given time or under certain environmental conditions.
Proteomics represents the genome at work and is a dynamic process.
Proteomics can be divided into expression proteomics, the study of global changes in protein expression, and cell-map proteomics, the systematic study of protein-protein interactions through the isolation of protein complexes (Blackstock and Weir 1999). Proteins expressed by an organism change during growth, disease, and the death of cells and tissues. Modifications of proteins that occur during and after their synthesis, such as the attachment of sugarresidues or lipids, change the proteome complement. The minimum proteome size can be calculated from the size and 2-D polyacrylamide gel electrophoresis (2-D PAGE) separated proteins. Proteomics is based on leading edge technological capability for.undertaking the mass screening of proteins and their post-translational modifications in whole organisms as well as in their tissues in normal and diseased states.
There are three main steps in proteome research:
§ Separation of individual proteins by 2-D polyacrylamide gel electrophoresis (2-D PAGE).
§ Identification by mass spectrometry or N-terminal sequencing of individual proteins recovered from the gel.
§ Storage, manipulation, and comparison of the data using bioinformatics.
Some scientists do not like the term proteomics and continue to use terms describing various technologies for proteins such as protein separation, etc. However, there is a distinction to be made between the molecular function of an isolated protein and the function of that protein in the complex cellular environment as studied by proteomic technologies. Proteomics attempts to catalog and characterize these proteins, compare variations in their expression levels in health and disease, study their interactions, and identify their functional roles. Proteomics is not the study of individual proteins as has been done traditionally, but rather in an automated, large-scale manner which requires new technologies and considerable effort is currently being devoted to the development of novel tools.
Proteomics will contribute greatly to our understanding of gene function in the post-genomic era. Differential display proteomics for comparison of protein levels has potential application in a wide range of diseases Because it is often difficult to predict the function of a protein based on homology to other proteins or even their three-dimensional structure, determination of components of a protein complex or of a cellular structure is central in functional analysis. This aspect of proteomic studies is perhaps the area of greatest promise (Pandey and Mann 2000). After the revolution in molecular biology exemplified by the ease of cloning by DNA methods, proteomics will add to our understanding of the biochemistry of proteins, processes and pathways for years to come.
Proteomics will also play an important role for drug discovery and development (Müllner et al 1998). Proteomics is the link between genes, proteins and disease. Many of the best-selling drugs either act by targeting proteins or are proteins. In addition, many molecular markers of disease, the basis of diagnostics, are proteins Patterns of protein expression can be used as a guide to drug design. Application of proteomics to study underlying pharmaceutical mechanisms and use these for drug development is referred to as pharmaceutical proteomics. Unlike classical genomic approaches that discover genes related to a disease, proteomics could characterize the disease process directly by finding sets of proteins (pathways or clusters) that together participate in causing it. The same technology is used to study the effects of candidate drugs intended to reverse a disease process.
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