FORCECHAPERONESProject reference: 329308
Funded under :
Chaperones mediated mechanical protein folding
Total cost:EUR 221 606,4
EU contribution:EUR 221 606,4
Coordinated in:United Kingdom
Topic(s):FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development"
Call for proposal:FP7-PEOPLE-2012-IEFSee other projects for this call
Funding scheme:MC-IEF - Intra-European Fellowships (IEF)
The main goal of this proposal is to understand the molecular mechanism by which proteins equilibrate under the effect of a constant stretching force and the effect of molecular chaperones in the mechanical folding of an individual protein. We will use the newly developed single molecule force-clamp spectroscopy technique to elucidate the conformational dynamics of a single refolding protein during its individual folding trajectory from highly extended states. A key feature of mechanical folding experiments is that the different conformations visited by the folding polypeptide can be unambiguously identified according to their distinct mechanical stability. The final folding transition is identified by the full recovery of the protein mechanical stability. These single molecule experiments have highlighted the conformational richness encountered along the folding pathway of an individual protein. A missing keystone in the accepted folding picture lies in understanding the molecular mechanisms by which some proteins fail to recover their natively folded conformation, triggering the aggregation process. Using a single molecule approach, here we aim at identifying the individual step along the folding pathway that prevents culmination of successful folding. In this vein, while much has been discovered about mechanical folding in the last years, the question of how chaperones will help the mechanical folding process remained elusive. Within a multidisciplinary approach, here we propose a series of innovative experiments to directly probe the effect of force on the function of an individual folding polypeptide in the absence or presence of molecular chaperones, of common occurrence in nature.
EU contribution: EUR 221 606,4
WC2R 2LS LONDON
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