Spectroscopic conformational studies of prion protein isoforms and the mechanism of transformation

Abstract

The agent responsible for transmission of spongiform encephalopathies (prion diseases) has unique biological and physical properties, and its essential component is the prion protein (scrapie amyloid). The recent developments in structural chemistry and molecular biology of the prion protein provide strong evidence for the central role of an abnormal post-translational protein folding mechanism in the transmission and pathogenesis of disease. During the course of disease, the normal chromosomal PrP gene product containing a predominantly α-helical secondary structure is transformed into a protein with more secondary structure in β-sheets. As a result, the protein acquires different physical properties and the ability to form amyloid. Understanding this apparently conformational conversion mechanism may advance the investigation of other neurodegenerative disorders and brain amyloidoses. Here we review current knowledge of the structural chemistry of the prion protein and explore the mechanism of its replication.