A universal protein-protein interaction motif in the eubacterial DNA replication and repair systems
Date
2001
Authors
Dalrymple, Brian Paul
Kongsuwan, Kritaya
Wijffels, Gene
Dixon, Nicholas
Jennings, Peter Andrew
Journal Title
Journal ISSN
Volume Title
Publisher
National Academy of Sciences (USA)
Abstract
The interaction between DNA polymerases and sliding clamp proteins confers processivity in DNA synthesis. This interaction is critical for most DNA replication machines from viruses and prokaryotes to higher eukaryotes. The clamp proteins also participate in a variety of dynamic and competing protein-protein interactions. However, clamp-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 clamp (the β subunit of Escherichia coli DNA polymerase III holoenzyme). Representatives of this motif are present in most sequenced members of the eubacterial DnaE, PoIC, PoIB, 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 clamp binding motifs suggests that the basic interactions have been conserved across the evolutionary landscape.
Description
Keywords
Keywords: bacterial DNA; DNA polymerase; article; binding site; DNA repair; DNA replication; DNA synthesis; Escherichia coli; Eubacterium; nonhuman; peptide analysis; priority journal; protein protein interaction; Amino Acid Sequence; Bacterial Proteins; Binding Si
Citation
Collections
Source
PNAS - Proceedings of the National Academy of Sciences of the United States of America
Type
Journal article
Book Title
Entity type
Access Statement
License Rights
Restricted until
2037-12-31