Thermotolerance Requires Refolding of Aggregated Proteins by Substrate Translocation through the Central Pore of ClpB
2004; Cell Press; Volume: 119; Issue: 5 Linguagem: Inglês
10.1016/j.cell.2004.11.027
ISSN1097-4172
AutoresJimena Weibezahn, Peter Tessarz, Christian Schlieker, Regina Zahn, Željka Maglica, Sukyeong Lee, Hanswalter Zentgraf, Eilika Weber‐Ban, David A. Dougan, Francis Tsai, Axel Mogk, Bernd Bukau,
Tópico(s)Protein Structure and Dynamics
ResumoCell 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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