PMID:15611053
| Citation |
Su'etsugu, M, Shimuta, TR, Ishida, T, Kawakami, H and Katayama, T (2005) Protein associations in DnaA-ATP hydrolysis mediated by the Hda-replicase clamp complex. J. Biol. Chem. 280:6528-36 |
|---|---|
| Abstract |
In Escherichia coli, the activity of ATP-bound DnaA protein in initiating chromosomal replication is negatively controlled in a replication-coordinated manner. The RIDA (regulatory inactivation of DnaA) system promotes DnaA-ATP hydrolysis to produce the inactivated form DnaA-ADP in a manner depending on the Hda protein and the DNA-loaded form of the beta-sliding clamp, a subunit of the replicase holoenzyme. A highly functional form of Hda was purified and shown to form a homodimer in solution, and two Hda dimers were found to associate with a single clamp molecule. Purified mutant Hda proteins were used in a staged in vitro RIDA system followed by a pull-down assay to show that Hda-clamp binding is a prerequisite for DnaA-ATP hydrolysis and that binding is mediated by an Hda N-terminal motif. Arg(168) in the AAA(+) Box VII motif of Hda plays a role in stable homodimer formation and in DnaA-ATP hydrolysis, but not in clamp binding. Furthermore, the DnaA N-terminal domain is required for the functional interaction of DnaA with the Hda-clamp complex. Single cells contain approximately 50 Hda dimers, consistent with the results of in vitro experiments. These findings and the features of AAA(+) proteins, including DnaA, suggest the following model. DnaA-ATP is hydrolyzed at a binding interface between the AAA(+) domains of DnaA and Hda; the DnaA N-terminal domain supports this interaction; and the interaction of DnaA-ATP with the Hda-clamp complex occurs in a catalytic mode. |
| Links |
PubMed Online version:10.1074/jbc.M412060200 |
| Keywords |
Adenosine Triphosphatases/isolation & purification; Adenosine Triphosphatases/metabolism; Adenosine Triphosphate/metabolism; Bacterial Proteins/metabolism; Binding Sites; Catalysis; DNA Helicases/metabolism; DNA Polymerase III/metabolism; DNA-Binding Proteins/metabolism; Dimerization; Escherichia coli Proteins/isolation & purification; Escherichia coli Proteins/metabolism; Hydrolysis; Multiprotein Complexes; Protein Binding; Protein Structure, Tertiary; Trans-Activators/metabolism |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.