Mapping protein family interactions: Intramolecular and intermolecular protein family interaction repertoires in the PDB and yeast

In the postgenomic era, one of the most interesting and important challenge s is to understand protein interactions on a large scale. The physical inte ractions between protein domains are fundamental to the workings of a cell: in multi-domain polypeptide chains, in multi-subunit proteins and in trans ient complexes between proteins that also exist independently. To study the large-scale patterns and evolution of interactions between protein domains , we view interactions between protein domains in terms of the interactions between structural families of evolutionarily related domains. This allows us to classify 8151 interactions betu een individual domains in the Protei n Data Bank and the yeast Saccharromyces cerevisiae in terms of 664 types o f interactions, between protein families. At least 51 interactions do not o ccur in the Protein Data Bank and can only be derived from the yeast data. The map of interactions between protein families has the form of a scale-fr ee network, meaning that most protein families only interact with one or tw o other families, while a few families are extremely versatile in their int eractions and are connected to many families. We observe that almost half o f all known families engage in interactions with domains from their own fam ily. We also see that the repertoires of interactions of domains within and between polypeptide chains overlap mostly for two specific types of protei n families: enzymes and same-family interactions. This suggests that differ ent types of protein interaction repertoires exist for structural, function al and regulatory reasons. (C) 2001 Academic Press.