Towards an understanding of protein-protein interaction network heirarchies. Analysis of DnaN-binding peptide motifs in members of protein families interacting with the eubacterial processivity clamp, the subunit of DNA Polymerase III

The consensus pentapeptide QL[SD]LF is a major component in the interaction of a number of families of proteins with the eubacterial DNA-clamp protein, DnaN (the β-subunit of DNA Polymerase III holoenzyme). Rankings of the motifs were established using the program MEME. The distribution of ranking of motifs in the PolC, DinB2 and UmuC protein families were shown to be significantly skewed to higher rankings (ie closer to the consensus), whilst motifs in the DinB1 and DnaE2 protein families were shown to be significantly skewed to lower rankings. Sub-division of the families on the basis of domain architecture, clustering of sequences, presence or absence of members of other DnaN-binding protein families and phylogenetic positions, has identified a number of relationships. Species containing PolC have DnaE1 and DinB1.1 proteins with significantly lower ranking motifs and MutS1 proteins with significantly higher-ranking motifs than average. These observations suggest that this group of eubacteria have a different hierarchy of interactions of DnaN-binding proteins from that in the majority of other species. Members of a new family of proteins of unknown function, Duf72, also have high-ranking putative DnaN-binding motifs. Motifs in a second new family containing putative DnaN-binding sites, DinB3, rank at the lower end.