Protein Interaction Networks

Excerpt

Protein interactions are an important layer of connectivity between cell components and cell processes. They allow the formation of protein complexes and mediate post-translational protein modifications. Disruption of protein-protein interactions may result in disruption of the cell component or process to which they contribute, compromising the cell viability or even leading to cell death. The study of protein interactions and their function has recently jumped to an organism scale, following the development of high-throughput yeast-two-hybrid screens mapping protein-protein interactions (–7) and affinity purification followed by mass spectrometry (MS) detecting protein complexes (8,9) (see Chapters 5, 6, and 7 for a thorough discussion of mass spectrometry and MS-based tissue imaging).

At the cellular level, protein interactions are represented by the protein interaction network, which is the union of all proteins and the interactions among them. The protein interaction network involves asking questions similar to those asked for specific protein interactions: how to map these interactions, which properties characterize them, how are these proteins connected to cell processes and functions, and what is the evolution of the protein network? These questions are now investigated at different levels, from specific protein-protein interactions, passing through protein complexes, signaling cascades, and other protein interaction network motifs, ending in the whole protein interaction network.

The role of the protein interaction network is beyond the network itself and it materializes through its interaction with other cellular networks. For example, the cell response to a change in environmental conditions requires the coordination between the signaling (a subnet of the protein interaction network), and the gene regulatory and metabolic networks. Consequently the study of protein interaction networks should be put in the context of the cell function. It is only in this way that the protein interaction network description can be transformed into better understanding and prediction of novel features and behavior. In this review I cover these different aspects of protein interaction networks. It is not intended to be an exhaustive review but is complemented by cited literature, including reviews of more specific topics.