Bacterial protein interaction networks: puzzle stones from solved complex structures add to a clearer picture.

Global scale studies of protein-protein interaction (PPI) networks have considerably expanded our view of how proteins act in the cell. In particular, bacterial "interactome" surveys have revealed that proteins can sometimes interact with a large number of protein partners and connect different cellular processes. More targeted, pathway-orientated PPI studies have also helped to propose functions for unknown proteins based on the "guilty by association" principle. However, given the immense repertoire of PPIs generated and the variability of PPI networks, more studies are required to understand the role(s) of these interactions in the cell. With the availability of bioinformatic analysis tools, transcriptomics and co-expression experiments for a given interaction, interactomes are being deciphered. More recently, functional and structural studies have been derived from these PPI networks. In this review, we will give a number of examples of how combining functional and structural studies into PPI networks has contributed to understanding the functions of some of these interactions. We discuss how interactomes now represent a unique opportunity to determine the structures of bacterial protein complexes on a large scale by the integration of multiple technologies.