Seminars Archive

Insights on Prion Protein Structure and Stability from Computer Simulations

Abstract
Conversion of the cellular form of the prion protein (PrP), PrPC, into its disease causing isoform, PrPSc, is the initial molecular event underlying several prion pathologies. The early events of PrPSc formation may involve a series of precursor species with a partially unstructured character. However, the presence of PrP unfolding intermediates still remains unclear. I will present a combined in silico/in vitro approach that our laboratory is following to address this issue. We have combined experimental measurements of PrP denaturation and several microsecond computer simulations of the refolding of PrP structure. Different PrP unfolding intermediates have been identified with a notably increased enthalpic stability with respect to the native conformer and featuring properties compatible with experimental measurements. HOST: Giuseppe Legname, ELETTRA & SISSA