Using Isotopically-Coded Hydrogen Peroxide as a Surface Modification Reagent for the Structural Characterization of Prion-Protein Aggregates

摘要

We were able to characterize differentially modified residues between PrPC and PrPβ form of prion using isotopically coded H_2O_2. The central element in the development of the prion diseases is the conversion of the native cellular prion protein (PrPC) into an aggregated pathological β-oligomeric (PrPβ) and fibril-forming isoform (PrPSc). The molecular mechanisms which lead to this conformational change, and the final structure of the aggregates, are still unknown. We are characterizing PrPC conformational changes using a combination of protein chemistry and mass spectrometry (MS). Chemical modification of the protein surface allows the determination of the regions of the proteins which are exposed to the solvent. We have applied surface modification combined with MS methods for the characterization of PrPC and PrPβ.