Tania Morán Luengo
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Tania Morán Luengo has a total of 6 co-authors. Here are the top co-authors by number of shared publications:
- Matthias P. Mayer
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Heidelberg, Germany
2 shared publications - Stefan G. D. Rudiger
Protein Chemistry of Disease, Department of Chemistry, Utrecht University, Padualaan 8, 3584CH Utrecht, The Netherlands
2 shared publications - Anna T. Hoekstra
Utrecht University
1 shared publication - Celia R. Berkers
Division Cell Biology, Metabolism & Cancer, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands
1 shared publication - Roman Kityk
Heidelberg University
1 shared publication - Toveann Ahlnäs
Utrecht University
1 shared publication
Latest Publications
- Open Access
Refolding activity of bacterial Hsp90 in vivo reveals ancient chaperoning function
The conserved molecular chaperones Hsp70 and Hsp90 play a key role in protein folding. Mechanistically, Hsp90 acts downstream from Hsp70 solving an Hsp70-inflicted folding block. It is unclear, though, when and to which extend the concerted action of this cascade becomes crucial in living organisms. Here we show that, in E. coli cells, Hsp90 dramatically improves protein refolding after heat stress while it is dispensable for de novo folding. We found that Hsp90 inhibition effectively reduced the refolding yields in vivo, leading to strongly reduced enzymatic activity of the paradigmatic chaperone client luciferase and broadly increased aggregation of the E. coli proteome. Additionally, the presence of Hsp90 during refolding reduces the net ATP consumption presumably by sparing the substrate binding-and-release cycles on Hsp70. This mechanism explains how the cooperation of Hsp90 with the Hsp70 chaperone system creates robust folding machinery in a sustainable manner. Together, we describe a general function for bacterial Hsp90 as a key factor of the folding cascade, which may be the ancient activity of this evolutionary conserved machine.
Open AccessRefolding activity of bacterial Hsp90 in vivo reveals ancient chaperoning function
The conserved molecular chaperones Hsp70 and Hsp90 play a key role in protein folding. Mechanistically, Hsp90 acts downstream from Hsp70 solving an Hsp70-inflicted folding block. It is unclear, though, when and to which extend the concerted action of this cascade becomes crucial in living organisms. Here we show that, in E. coli cells, Hsp90 dramatically improves protein refolding after heat stress while it is dispensable for de novo folding. We found that Hsp90 inhibition effectively reduced the refolding yields in vivo, leading to strongly reduced enzymatic activity of the paradigmatic chaperone client luciferase and broadly increased aggregation of the E. coli proteome. Additionally, the presence of Hsp90 during refolding reduces the net ATP consumption presumably by sparing the substrate binding-and-release cycles on Hsp70. This mechanism explains how the cooperation of Hsp90 with the Hsp70 chaperone system creates robust folding machinery in a sustainable manner. Together, we describe a general function for bacterial Hsp90 as a key factor of the folding cascade, which may be the ancient activity of this evolutionary conserved machine.
- Open Access
Breaking the Deadlock of Molecular Chaperones
Protein folding in the cell requires ATP-driven chaperone machines. It is poorly understood, however, how these machines fold proteins. Here we propose that the conserved Hsp70 and Hsp90 chaperones support formation of the folding nucleus by providing a gradient of decreasing hydrophobicity. Early on the folding pathway Hsp70 uses its highly hydrophobic binding pocket to recover a stalled, unproductive folding intermediate. The aggressive nature of Hsp70 action, however, blocks productive folding by grabbing hydrophobic, core-forming segments. This precludes on-pathway nucleation at high, physiological Hsp70 levels. Transfer to the less hydrophobic Hsp90 enables the intermediate to resume forming its folding nucleus. Subsequently, the protein enters a spontaneous folding trajectory towards its native state, independent of the ATPase activities of both Hsp70 and Hsp90. Our findings provide a general mechanistic concept for chaperoned protein folding.
Open AccessBreaking the Deadlock of Molecular Chaperones
Protein folding in the cell requires ATP-driven chaperone machines. It is poorly understood, however, how these machines fold proteins. Here we propose that the conserved Hsp70 and Hsp90 chaperones support formation of the folding nucleus by providing a gradient of decreasing hydrophobicity. Early on the folding pathway Hsp70 uses its highly hydrophobic binding pocket to recover a stalled, unproductive folding intermediate. The aggressive nature of Hsp70 action, however, blocks productive folding by grabbing hydrophobic, core-forming segments. This precludes on-pathway nucleation at high, physiological Hsp70 levels. Transfer to the less hydrophobic Hsp90 enables the intermediate to resume forming its folding nucleus. Subsequently, the protein enters a spontaneous folding trajectory towards its native state, independent of the ATPase activities of both Hsp70 and Hsp90. Our findings provide a general mechanistic concept for chaperoned protein folding.