The phenomenon of protein superstructural polymorphism has become the subject of increased research activity. Besides the relevance to explain the existence of multiple prion strains, such activity is partly driven by the recent finding that in many age-related neurodegenerative diseases highly ordered self-associated forms of peptides and proteins might be the structural basis of prion-like processes and strains giving rise to different disease phenotypes. Biophysical studies of prion strains have been hindered by a lack of tools to characterize inherently noncrystalline, heterogeneous and insoluble proteins. A description of the pressure response of prion quaternary structures might change this picture. This is because applying pressure induces quaternary structural changes of PrP, such as misfolding and self-assembly. From the thermodynamics of these processes, structural features in terms of associated volume changes can then be deduced. We suggest that conformation-enciphered prion strains can be distinguished in terms of voids in the interfaces of the constituting PrP protomers and thus in their volumetric properties.
Keywords: amyloid; oligomer; pressure; prion; protein misfolding; strain.