Molecular chaperones DnaK and DnaJ share predicted binding sites on most proteins in the E. coli proteome
| Autor: | Sharan R. Srinivasan, Jason E. Gestwicki, Anne T. Gillies, Andrea D. Thompson, Lyra Chang |
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| Rok vydání: | 2012 |
| Předmět: |
endocrine system
Proteome Escherichia coli Proteins genetic processes Plasma protein binding Biology Protein Homeostasis medicine.disease_cause Article medicine HSP70 Heat-Shock Proteins Binding site Molecular Biology Escherichia coli Genetics Binding Sites HSP40 Heat-Shock Proteins Folding (chemistry) Biochemistry biological sciences bacteria Molecular Chaperones Protein Binding Biotechnology |
| Zdroj: | Molecular BioSystems. 8:2323 |
| ISSN: | 1742-2051 1742-206X |
| Popis: | In Escherichia coli, the molecular chaperones DnaK and DnaJ cooperate to assist the folding of newly synthesized or unfolded polypeptides. DnaK and DnaJ bind to hydrophobic motifs in these proteins and also each other to promote folding. This system is thought to be sufficiently versatile to act on the entire proteome, which creates interesting challenges in understanding the large-scale, ternary interactions between DnaK, DnaJ and their thousands of potential substrates. To address this question, we computationally predicted the number and frequency of DnaK- and DnaJ-binding motifs in the E. coli proteome, guided by free energy-based binding consensus motifs. This analysis revealed that nearly every protein is predicted to contain multiple DnaK- and DnaJ-binding sites, with the DnaJ sites occurring approximately twice as often. Further, we found that an overwhelming majority of the DnaK sites partially or completely overlapped with the DnaJ-binding motifs. It is well known that high concentrations of DnaJ inhibit DnaK-DnaJ-mediated refolding. The observed overlapping binding sites suggest that this phenomenon may be explained by an important balance in the relative stoichiometry of DnaK and DnaJ which determines whether they bind synergistically or competitively. To test this idea, we measured the chaperone-assisted folding of two denatured substrates and found that the distribution of predicted DnaK- and DnaJ-binding sites was indeed a good predictor of the optimal stoichiometry required for folding. These studies provide insight into how DnaK and DnaJ might cooperate to maintain global protein homeostasis. |
| Databáze: | OpenAIRE |
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