PMID:15550247
| Citation |
Weibezahn, J, Tessarz, P, Schlieker, C, Zahn, R, Maglica, Z, Lee, S, Zentgraf, H, Weber-Ban, EU, Dougan, DA, Tsai, FT, Mogk, A and Bukau, B (2004) Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB. Cell 119:653-65 |
|---|---|
| Abstract |
Cell survival under severe thermal stress requires the activity of the ClpB (Hsp104) AAA+ chaperone that solubilizes and reactivates aggregated proteins in concert with the DnaK (Hsp70) chaperone system. How protein disaggregation is achieved and whether survival is solely dependent on ClpB-mediated elimination of aggregates or also on reactivation of aggregated proteins has been unclear. We engineered a ClpB variant, BAP, which associates with the ClpP peptidase and thereby is converted into a degrading disaggregase. BAP translocates substrates through its central pore directly into ClpP for degradation. ClpB-dependent translocation is demonstrated to be an integral part of the disaggregation mechanism. Protein disaggregation by the BAP/ClpP complex remains dependent on DnaK, defining a role for DnaK at early stages of the disaggregation reaction. The activity switch of BAP to a degrading disaggregase does not support thermotolerance development, demonstrating that cell survival during severe thermal stress requires reactivation of aggregated proteins. |
| Links |
PubMed Online version:10.1016/j.cell.2004.11.027 |
| Keywords |
Cell Survival/genetics; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/genetics; Escherichia coli Proteins/isolation & purification; Escherichia coli Proteins/metabolism; HSP70 Heat-Shock Proteins/genetics; HSP70 Heat-Shock Proteins/metabolism; Heat-Shock Proteins/genetics; Heat-Shock Proteins/isolation & purification; Heat-Shock Proteins/metabolism; Heat-Shock Response/genetics; Molecular Chaperones/genetics; Molecular Chaperones/metabolism; Molecular Motor Proteins; Molecular Sequence Data; Multiprotein Complexes/genetics; Multiprotein Complexes/metabolism; Protein Engineering; Protein Folding; Protein Transport/physiology; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid |
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