Probing PrPSc structure using chemical cross-linking and mass spectrometry: evidence of the proximity of Gly90 amino termini in the PrP 27-30 aggregate.

Elucidation of the structure of PrP(Sc) continues to be one of the most important and difficult challenges in prion research. This task, essential for gaining an understanding of the basis of prion infectivity, has been hampered by the insoluble, aggregated nature of this molecule. We used a combination of chemical cross-linking, proteolytic digestion, and mass spectrometry (MALDI-TOF and nanoLC-ESI-QqTOF), in an attempt to gain structural information about PrP 27-30 purified from the brains of Syrian hamsters infected with scrapie.