On the association between domain-domain interactions and protein-protein interactions

Hanah Margalit
The Hebrew university of Jerusalem

Recently, there has been much interest in relating domain-domain interactions to protein-protein interactions and vice versa, in an attempt to understand the molecular basis of protein-protein interactions. To this end we mapped structurally-derived interacting domain pairs onto the cellular protein interaction networks of different organisms and demonstrated that there is a catalogue of domain pairs that is used for mediating various interactions in the cell. Furthermore, these interacting domain pairs occur frequently in protein complexes. A comparison of the repertoires of the interacting domain pairs in the networks of five organisms (from Escherichia coli to human) showed that many of them are evolutionary conserved. Our results indicate that different organisms use the same "building blocks" for protein-protein interactions, suggesting that the functionality of many domain pairs as mediating protein interactions is maintained in evolution. Can these domain-pairs be used for predicting protein-protein interactions? Our initial analysis suggests that within domain pairs that are capable of mediating interactions there are 'fine-tuners' that determine whether or not an interaction will be fulfilled.