Specificity and Stability in Topology of Protein Networks

Abstract

Molecular networks guide the biochemistry of a living cell on multiple levels: its metabolic and signalling pathways are shaped by the network of interacting proteins, whose production, in turn, is controlled by the genetic regulatory network. To address topological properties of these two networks we quantify correlations between connectivities of interacting nodes and compare them to a null model of a network, in which al links were randomly rewired. We find that for both interaction and regulatory networks, links between highly connected proteins are systematically suppressed, while those between a highly-connected and low-connected pairs of proteins are favored. This effect decreases the likelihood of cross talk between different functional modules of the cell, and increases the overall robustness of a network by localizing effects of deleterious perturbations.With the growth of experimental information about basic biochemical mechanisms of life, molecular networks operating in living cells are becoming better defined. Direct physical interactions between pairs of proteins form one such network. It serves as a backbone for functional and structural relationships among its nodes and defines pathways for the propagation of various signals such as phosphorylation and allosteric regulation of proteins. The information about specific binding of proteins to each other has recently grown by an unprecedented amount as a result of high throughput two-hybrid experiments [1,2]. The production and degradation of proteins participating in the interaction network is controlled by the genetic regulatory network of the cell formed by all pairs of proteins in which the first protein directly regulates the abundance of the second. The majority of known cases of such regulation happens at the level of transcription, in which a transcription fac-1

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