Objective 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. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingnatural sciencesphysical sciencesopticsspectroscopy Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2012-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2012-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator KING'S COLLEGE LONDON EU contribution € 221 606,40 Address STRAND WC2R 2LS London United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Administrative Contact Paul Labbett (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data