Objectif Protein folding, the process by which a protein assumes its three-dimensional shape, is one of the basic unsolved problems of biophysical and biochemical research. Many of the structural changes taking place during protein folding, especially during the early stages, are as yet poorly understood. This is because high-resolution structural techniques generally lack the time resolution necessary for observation of folding dynamics, whereas methods that have the required time resolution generally lack structural specificity. We propose an experimental approach that combines the structure-sensitivity of multi-dimensional NMR with the ultrafast time resolution of optical techniques. To do this, we use two-dimensional optical spectroscopy (in particular, two-dimensional optical spectroscopy and time-resolved vibrational circular dichroism) in combination with site-specific labeling of proteins. This will make it possible to obtain a structurally and temporally resolved picture of protein folding, which can be regarded as a 'molecular movie' of the folding process. With the proposed method, we will investigate structural changes during protein folding at increasing levels of complexity: from the dynamics of alpha-helix nucleation, to the formation and structural characteristics of intermediate states in small globular proteins and complex beta-sheet topologies, to the nature of biologically functional, short-lived unfolded states in signalling proteins. At each of these levels of complexity, the proposed method will be used to unravel the mechanisms behind the respective folding events. Champ scientifique natural sciencesmathematicspure mathematicstopologyhumanitiesartsmodern and contemporary artcinematographynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingnatural sciencesphysical sciencesopticsspectroscopy Mots‑clés two-dimensional optical spectroscopy Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-PE3 - ERC Starting Grant - Condensed matter physics Appel à propositions ERC-2007-StG Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil UNIVERSITEIT VAN AMSTERDAM Contribution de l’UE € 1 716 321,00 Adresse SPUI 21 1012WX Amsterdam Pays-Bas Voir sur la carte Région West-Nederland Noord-Holland Groot-Amsterdam Type d’activité Higher or Secondary Education Establishments Chercheur principal Sander Woutersen (Dr.) Contact administratif Jo Lansbergen (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITEIT VAN AMSTERDAM Pays-Bas Contribution de l’UE € 1 716 321,00 Adresse SPUI 21 1012WX Amsterdam Voir sur la carte Région West-Nederland Noord-Holland Groot-Amsterdam Type d’activité Higher or Secondary Education Establishments Chercheur principal Sander Woutersen (Dr.) Contact administratif Jo Lansbergen (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
