Abstract
BackgroundThe functions of a eukaryotic cell are largely performed by multi-subunit protein complexes that act as molecular machines or information processing modules in cellular networks. An important problem in systems biology is to understand how, in general, these molecular machines respond to perturbations.ResultsIn yeast, genes that inhibit growth when their expression is reduced are strongly enriched amongst the subunits of multi-subunit protein complexes. This applies to both the core and peripheral subunits of protein complexes, and the subunits of each complex normally have the same loss-of-function phenotypes. In contrast, genes that inhibit growth when their expression is increased are not enriched amongst the core or peripheral subunits of protein complexes, and the behaviour of one subunit of a complex is not predictive for the other subunits with respect to over-expression phenotypes.ConclusionWe propose the principle that the overall activity of a protein complex is in general robust to an increase, but not to a decrease in the expression of its subunits. This means that whereas phenotypes resulting from a decrease in gene expression can be predicted because they cluster on networks of protein complexes, over-expression phenotypes cannot be predicted in this way. We discuss the implications of these findings for understanding how cells are regulated, how they evolve, and how genetic perturbations connect to disease in humans.
Highlights
The functions of a eukaryotic cell are largely performed by multi-subunit protein complexes that act as molecular machines or information processing modules in cellular networks
Genes that reduce fitness when under- but not overexpressed are enriched amongst protein complexes Most essential functions of the eukaryotic cell are performed by multi-subunit protein complexes
A simple principle for the robustness of protein complex function and its implications for systems biology In summary we have shown that in yeast reducing the expression of any individual subunit of a protein complex that performs an essential function under laboratory conditions is likely to disrupt the function of that complex
Summary
The functions of a eukaryotic cell are largely performed by multi-subunit protein complexes that act as molecular machines or information processing modules in cellular networks. The proteome of a eukaryotic cell is largely organized as a collection of multi-subunit protein complexes [1,2,3,4]. These complexes are defined empirically by the stable association of their subunits during biochemical purification [3,4] and act as molecular machines [5] or information processing modules [6] in cellular networks. We show here that this is not true for changes (page number not for citation purposes)
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