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Thermotolerance Requires Refolding of Aggregated Proteins by Substrate Translocation through the Central Pore of ClpB
Open accessAbstract
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.
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Citations
Cited by
Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging
Morimoto, R. I. (2008) · Genes & Development · doi:10.1101/gad.1657108 · Cited by 872
Leiman, P. G., Basler, M., Ramagopal, U. A., Bonanno, J. B., Sauder, J. M., Pukatzki, S., Burley, S. K., Almo, S. C., & Mekalanos, J. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813360106 · Cited by 658
Protein Quality Control in the Cytosol and the Endoplasmic Reticulum: Brothers in Arms
Buchberger, A., Bukau, B., & Sommer, T. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.10.001 · Cited by 483
Self-citationChaperones in control of protein disaggregation
Liberek, K., Lewandowska, A., & Ziętkiewicz, S. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601970 · Cited by 425
A chemical toolkit for proteins — an expanded genetic code
Xie, J., & Schultz, P. G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2005 · Cited by 408
Metadata
- Authors
- Weibezahn, J., Tessarz, P., Schlieker, C., Zahn, R., Maglica, Z., Lee, S., Zentgraf, H., Weber-Ban, E. U., Dougan, D. A., Tsai, F. T. F., Mogk, A., & Bukau, B.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 119
- Issue
- 5
- Pages
- 653-665
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1998018574
- Cited by
- 459
- References
- 0
- FWCI
- 9.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Weibezahn, J., Tessarz, P., Schlieker, C., Zahn, R., Maglica, Z., Lee, S., Zentgraf, H., Weber-Ban, E. U., Dougan, D. A., Tsai, F. T. F., Mogk, A., & Bukau, B. (2004). Thermotolerance Requires Refolding of Aggregated Proteins by Substrate Translocation through the Central Pore of ClpB. Cell. https://doi.org/10.1016/j.cell.2004.11.027
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