PMID:14659744
| Citation |
Poon, GM and Macgregor, RB Jr (2004) A thermodynamic basis of DNA sequence selectivity by the ETS domain of murine PU.1. J. Mol. Biol. 335:113-27 |
|---|---|
| Abstract |
The ETS domain of the transcription factor PU.1 tolerates a large number of DNA cognate variants that differ exclusively in the sequences flanking a critical central consensus, 5'-GGAA-3'. We investigated the thermodynamics of site selection by the DNA-binding domain by following the PU.1 ETS/DNA equilibrium with a large set of cognate variants under various temperature and salt conditions by filter binding. Our results indicate that the stability of the ETS/DNA complex is quantitatively tied to variations in the change in heat capacity. Thermodynamic effects induced by changing Na(+) concentrations from 150 mM to 250 mM are complex and not readily interpreted by polyelectrolyte theory. We also extended our understanding of data from our previous investigation on energetic base-neighbour coupling, by dissecting the thermodynamic contributions underlying the observed free-energy coupling. In conjunction with available structural and biochemical data, we propose that site selectivity by the PU.1 ETS domain arises from differential protein/DNA contacts in the flanking sequences that modulate the orientation of the ETS recognition helix and trigger a coupled reduction in the flexibility observed in the unbound ETS domain. |
| Links | |
| Keywords |
Animals; Base Sequence; Binding Sites; DNA/chemistry; DNA/metabolism; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/metabolism; Mice; Osmolar Concentration; Pliability; Protein Binding; Protein Structure, Tertiary; Proto-Oncogene Proteins/chemistry; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-ets; Sodium/pharmacology; Temperature; Thermodynamics; Trans-Activators/chemistry; Trans-Activators/metabolism; Transcription Factors/chemistry |
| 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.