Publication
A universal protein-protein interaction motif in the eubacterial DNA replication and repair systems
Publisher:
Proceedings of the National Academy of Sciences
Date:
25-09-2001
DOI:
10.1073/PNAS.191384398
Abstract: The interaction between DNA polymerases and sliding cl proteins confers processivity in DNA synthesis. This interaction is critical for most DNA replication machines from viruses and prokaryotes to higher eukaryotes. The cl proteins also participate in a variety of dynamic and competing protein–protein interactions. However, cl -protein binding sequences have not so far been identified in the eubacteria. Here we show from three lines of evidence, bioinformatics, yeast two-hybrid analysis, and inhibition of protein–protein interaction by modified peptides, that variants of a pentapeptide motif (consensus QL[SD]LF) are sufficient to enable interaction of a number of proteins with an archetypal eubacterial sliding cl (the β subunit of Escherichia coli DNA polymerase III holoenzyme). Representatives of this motif are present in most sequenced members of the eubacterial DnaE, PolC, PolB, DinB, and UmuC families of DNA polymerases and the MutS1 mismatch repair protein family. The component tripeptide DLF inhibits the binding of the α (DnaE) subunit of E. coli DNA polymerase III to β at μM concentration, identifying key residues. Comparison of the eubacterial, eukaryotic, and archaeal sliding cl binding motifs suggests that the basic interactions have been conserved across the evolutionary landscape.