PMID:15134440
| Citation |
Wijffels, G, Dalrymple, BP, Prosselkov, P, Kongsuwan, K, Epa, VC, Lilley, PE, Jergic, S, Buchardt, J, Brown, SE, Alewood, PF, Jennings, PA and Dixon, NE (2004) Inhibition of protein interactions with the beta 2 sliding clamp of Escherichia coli DNA polymerase III by peptides from beta 2-binding proteins. Biochemistry 43:5661-71 |
|---|---|
| Abstract |
The sliding clamp of the Escherichia coli replisome is now understood to interact with many proteins involved in DNA synthesis and repair. A universal interaction motif is proposed to be one mechanism by which those proteins bind the E. coli sliding clamp, a homodimer of the beta subunit, at a single site on the dimer. The numerous beta(2)-binding proteins have various versions of the consensus interaction motif, including a related hexameric sequence. To determine if the variants of the motif could contribute to the competition of the beta-binding proteins for the beta(2) site, synthetic peptides derived from the putative beta(2)-binding motifs were assessed for their abilities to inhibit protein-beta(2) interactions, to bind directly to beta(2), and to inhibit DNA synthesis in vitro. A hierarchy emerged, which was consistent with sequence similarity to the pentameric consensus motif, QL(S/D)LF, and peptides containing proposed hexameric motifs were shown to have activities comparable to those containing the consensus sequence. The hierarchy of peptide binding may be indicative of a competitive hierarchy for the binding of proteins to beta(2) in various stages or circumstances of DNA replication and repair. |
| Links |
PubMed Online version:10.1021/bi036229j |
| Keywords |
Amino Acid Motifs; Binding, Competitive; Carrier Proteins/chemistry; Carrier Proteins/metabolism; Computer Simulation; Consensus Sequence; DNA Polymerase III/antagonists & inhibitors; DNA Polymerase III/chemistry; DNA Polymerase III/metabolism; DNA, Bacterial/antagonists & inhibitors; DNA, Bacterial/biosynthesis; Dimerization; Escherichia coli Proteins/antagonists & inhibitors; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/metabolism; Models, Molecular; Oligopeptides/chemistry; Oligopeptides/metabolism; Protein Interaction Mapping/methods; Protein Subunits/chemistry; Protein Subunits/metabolism; Surface Plasmon Resonance |
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