Skip to main content

Direct Investigation of a Folding Energy Landscape and Its Implications for the Unexplained Folding Behaviour of Spectrin Domains

Objective

Spectrin domains R15, R16 and R17 are found in tandem arrays in proteins of the cytoskeleton, and spectrin itself is believed to be responsible for maintaining the shape of erythrocites by imparting elasticity to the cell membrane. These three domains share virtually identical structure, stability, contact order, helical propensity, and transition state structure. However, in spite of the striking structural resemblance and the apparently common function, these proteins fold to their native conformation with a speed that varies over more than three orders of magnitude. Why? There is some evidence to suggest that such diversity originates from energy landscape “roughness”. Slow folding domains (R16 and R17) appear to have rough energy landscapes, whereas the fast folding domain R15 has a smooth energy landscape. By means of a novel, single-molecule spectroscopic technique developed by Prof. Benjamin Schuler at the Department of Biochemistry of the University of Zurich, I want to test this hypothesis, investigating directly the energy landscape of these homologous spectrin domains, quantifying the roughness of their energy landscape, and discover its sequence determinants. This research is the first direct investigation of energy landscape roughness of proteins for which this feature is believed to clearly affect the folding rate. These studies could not only result in substantial conceptual progress in the field of protein folding, providing a missing link between theory and experiment, but also lead to further developments of the single-molecule spectroscopy for biophysical investigation in general

Field of science

  • /natural sciences/chemical sciences/analytical chemistry/spectroscopy
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/biochemistry

Call for proposal

FP7-PEOPLE-IEF-2008
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

UNIVERSITAT ZURICH
Address
Ramistrasse 71
8006 Zürich
Switzerland
Activity type
Other
EU contribution
€ 180 801,44
Administrative Contact
Benjamin Schuler (Prof.)