Chapter 3: Protein Structure and Function

Proteomics Is the Study of All or a Large Subset of Proteins in a Biological System

The advent of genomics (sequencing of genomic DNA and its associated technologies, such as simultaneous analysis of the levels of all mRNAs in cells and tissues) clearly showed that a global, or systems, approach to biology could provide unique and highly valuable insights. Many scientists recognized that a global analysis of the proteins in biological systems had the potential for equally valuable contributions to our understanding. Thus a new field was born—proteomics. Proteomics is the systematic study of the amounts, modifications, interactions, localization, and functions of all or subsets of proteins at the whole-organism, tissue, cellular, and subcellular levels.

A number of broad questions are addressed in proteomic studies:

In a given sample (whole organism, tissue, cell, subcellular compartment), what fraction of the whole proteome is expressed (i.e., which proteins are present)?
Of those proteins present in the sample, what are their relative abundances?
What are the relative amounts of the different splice forms and chemically modified forms (e.g., phosphorylated, methylated, fatty acylated) of the proteins?
Which proteins are present in large multiprotein complexes, and which proteins are in each complex? What are the functions of these complexes, and how do they interact?
When the state (e.g., growth rate, stage of cell cycle, differentiation, stress level) of a cell changes, do the proteins in the cell, or those secreted from the cell, change in a characteristic (fingerprint-like) pattern? Which proteins change, and how (relative amounts, modifications, splice forms, etc.)? [Answering these questions requires a form of protein expression profiling that complements the transcriptional (mRNA) profiling discussed in Chapter 9.]
Can such fingerprint-like changes be used for diagnostic purposes? For example, do certain cancers or heart disease cause characteristic changes in blood proteins? Can the proteomic fingerprint help determine if a given cancer is resistant or sensitive to a particular chemotherapeutic drug? [Proteomic fingerprints can also be the starting point for studies of the mechanisms underlying the change of state. Proteins (and other biomolecules) that show changes that are diagnostic of a particular state are called biomarkers.]
Can changes in the proteome help define targets for drugs or suggest mechanisms by which a drug might induce toxic side effects? (If so, it might be possible to engineer modified versions of the drug with fewer side effects.)

These are just a few of the questions that can be addressed using proteomics. The methods used to answer these questions are as diverse as the questions themselves, and their numbers are growing rapidly.