Normal Modes of Prion Proteins: From Native to Infectious Particle

Prion proteins (PrP) are the infectious agent in transmissible spongiform encephalopathies (i.e., mad cow disease). To be infectious, prion proteins must undergo a conformational change involving a decrease in a-helical content along with an increase in beta-strand content. This conformational change was evaluated by means of elastic normal modes. Elastic normal modes show a diminution of two a-helices by one and two residues, as well as an extension of two beta-strands by three residues each, which could instigate the conformational change. The conformational change occurs in a region that is compatible with immunological studies, and it is observed more frequently in mutant prions that are prone to conversion than in wild-type prions because of differences in their starting structures, which are amplified through normal modes. These findings are valuable for our comprehension of the conversion mechanism associated with the conformational change in prion proteins.