Proteomics 8/1/03. By Richard Twyman The global study of proteins: their structure, expression and interactions with other molecules.

The human genome contains the complete set of genes required to build a functional human being. However, the genome is only a source of information. In order to function, it must be expressed.

The transcription of genes is the first stage of gene expression and is followed by the translation of messenger RNA to produce proteins. The proteome is the complete set of proteins produced by the genome at any one time.

The proteome is much more complex than either the genome or the transcriptome (see Transcriptomics ). This is because each protein can be chemically modified in different ways after synthesis. Many proteins have carbohydrate groups added to them. Others are phosphorylated or acetylated or methylated.

The proteome is also very dynamic. Most of our cells contain the same genome regardless of the cell type, developmental stage or environmental conditions. The proteome, however, varies considerably in these differing circumstances due to different patterns of gene expression and different patterns of protein modification.

Proteomics, the study of the proteome, is important because proteins represent the actual functional molecules in the cell. When mutations occur in the DNA, it is the proteins that are ultimately affected. Drugs, when they have beneficial effects, do so by interacting with proteins. Proteomics therefore covers a number of different aspects of protein function, including the following:

• Structural proteomics, the large-scale analysis of protein structures. Protein structure comparisons can help to identify the functions of newly discovered genes. Structural analysis can also show where drugs bind to proteins and where proteins interact with each other. This is achieved using technologies such as X-ray crystallography and NMR spectroscopy .
• Expression proteomics, the large-scale analysis of protein expression. This can help to identify the main proteins found in a particular sample and proteins differentially expressed in related samples, such as diseased vs healthy tissue. A protein found only in a diseased sample may represent a useful drug target or diagnostic marker. Proteins with similar expression profiles may also be functionally related. Technologies such as two-dimensional polyacrylamide gel electrophoresis and mass spectrometry are used here.
• Interaction proteomics, the large-scale analysis of protein interactions. The characterisation of protein-protein interactions helps to determine protein functions and can also show how proteins assemble in larger complexes. Technologies such as affinity purification, mass spectrometry and the yeast two-hybrid system are particularly useful.

The techniques for proteome analysis are not as straightforward as those used in transcriptomics. However, the advantage of proteomics is that the real functional molecules of the cell are being studied. Strong gene expression, resulting in an abundant mRNA, does not necessarily mean that the corresponding protein is also abundant or indeed active in the cell.