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Content archived on 2024-06-18

Chaperones mediated mechanical protein folding

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 (EuroSciVoc)

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2012-IEF
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Funding Scheme

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MC-IEF - Intra-European Fellowships (IEF)

Coordinator

KING'S COLLEGE LONDON
EU contribution
€ 221 606,40
Address
STRAND
WC2R 2LS London
United Kingdom

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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