Fibrillation of proteins

Bente Vestergaard

Small Angle Scattering is uniquely suitable for investigating mixtures of proteins. In fact, just about any other structural method is severely compromised in such cases. If we have some prior knowledge regarding our mixtures, or if the systems are only relatively complex, from small angle scattering data, we can extract information about individual species that are present in a given mixture. Protein fibrillation is a good example of a system that we would very much like to investigate, but where we have quite complicated mixtures of different protein species in solution at a given time point. Protein fibrils are formed from thousands and thousands of non-natively folded proteins, that associate over time. We have numerous examples of investigations of such systems, where we follow the development from native protein, over the process and to the mature fibrils. In some cases we have been able to isolate the scattering signal from an intermediate non-native oligomeric species. Such an oligomeric species has been suggested to be the main cause of the cytotoxicity which is associated with the amyloid diseases (such as e.g. Parkinsons or Alzheimers disease). Our SAXS data have also provided us with some unexpected information about the solutions of mature fibrils. This information indicates how the fibril surface may assist in accelerating the process of fibrillation, a process known as secondary nucleation.

Vestergaard, B., Groenning, M., Roessle, M., Kastrup, J.S., van de Weert, M., Flink, J.M., Frokjaer, S., Gajhede, M., Svergun, D.I. (2007) A helical structural nucleus is the primary elongating unit of insulin amyloid fibrils. PLoS Biology 5(5), e134.

Date/time: Saturday, 30 October, 14:00