Progress of modern day biology will require understanding and harnessing the network of interactions between genes, proteins and the functional systems that these produce. Given the complexity of even the most primitive living organism, and our still very limited knowledge, it is unreasonable to expect that we might, in the near or even medium term, reach such understanding at the level of an entire cell. A prequesite for this goal is an understanding of the biological function of the complete set of genes and proteins within genomes (post-genomic biology). Proteins rarely act alone: they typically interact with other macromolecules to perform particular cellular tasks. The resulting functional assemblies (complexes) are more than the sum of their parts. They have a function that is not easily understood by even the most systematic analyses of single proteins. Thus the discovery and analysis of particular cellular protein complexes under physiological conditions provides key insights into their function, and takes the characterisation of the system well beyond the limits of other experiments. Prominent examples include the ribosome, the chaperonin GroEl/GroEs, the spliceosome, the cyclosome, the proteasome, the nuclear pore complex and the synaptosome. Analyses of results from genome- scale interaction discoveries in yeast show a clear tendency for many yeast assemblies to mirror their equivalents in animals, including the model organisms and man. Complexes essential for the cell overlap significantly, and represent the building blocks of a Eukaryotic core proteome covering basic cellular function. More importantly, those conserved between yeast and man will contribute significantly to the understanding of multifactorial diseases, particularly those related to key cellular processes. Elucidation of three-dimensional (3D structures for protein complexes will open new avenues to unravel the molecular pathology and physiology of #
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