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Molecular Movies of Protein Folding

Objective

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.

Field of science

  • /natural sciences/chemical sciences/analytical chemistry/spectroscopy
  • /humanities/arts/modern and contemporary art/film
  • /natural sciences/mathematics/pure mathematics/topology
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins

Call for proposal

ERC-2007-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

UNIVERSITEIT VAN AMSTERDAM
Address
Spui 21
1012WX Amsterdam
Netherlands
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 716 321
Principal investigator
Sander Woutersen (Dr.)
Administrative Contact
Jo Lansbergen (Ms.)

Beneficiaries (1)

UNIVERSITEIT VAN AMSTERDAM
Netherlands
EU contribution
€ 1 716 321
Address
Spui 21
1012WX Amsterdam
Activity type
Higher or Secondary Education Establishments
Principal investigator
Sander Woutersen (Dr.)
Administrative Contact
Jo Lansbergen (Ms.)