Fibrillation of proteins
University of Copenhagen, Denmark
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
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