Poster abstracts

Poster number 8 submitted by Tara George

Cross-seeding specificities of mammalian Y145Stop prion protein amyloids probed by solid-state NMR

Tara George (The Ohio State University), Theint Theint (The Ohio State University), Krystyna Surewicz (Case western Reserve University), Witold K. Surewicz (Case Western Reserve University), Christopher P. Jaroniec (The Ohio State University)

Abstract:
Prion diseases, a diverse group of transmissible fatal neurodegenerative disorders, are associated with aggregation of monomeric prion protein into fibrillar amyloid deposits. Two key features of mammalian prion propagation, strains and transmission barriers, are believed to be related to the three-dimensional structures of the prion amyloid aggregates. The prion strain and transmission barrier phenomena can be investigated in detail using Y145Stop prion protein (PrP23-144) as a model. Previous low-resolution studies have shown that the seeding specificities of mammalian PrP23-144 amyloids are correlated with the fibril conformation,1 and, more recently, we have used to solid-state NMR to show that human, mouse and Syrian hamster PrP23-144 amyloids adopt distinct core structures.2,3 Here, we use solid-state NMR to gain atomic level insight into cross-seeding reactions between the different PrP23-144 proteins, where amyloid formation by a monomeric protein from one species is seeded with preformed fibrils from another species. Remarkably, we find that in some cases conformational switching can be observed, where depending on the experimental conditions the structure of the final PrP23-144 amyloid can resemble either that obtained in unseeded reactions of the native parent protein or that of the fibril seed from a different species.

References:
1. Jones, E. M. and Surewicz, W. K. Fibril conformation as the basis of species and strain dependent seeding specificity of mammalian prion amyloids. Cell 121, 63-72 (2005).
2. Theint, T., Nadaud, P. S., Aucoin, D., Helmus, J. J., Pondaven, S. P., Surewicz, K., Surewicz, W. K. and Jaroniec, C. P. Species-dependent structural polymorphism of Y145Stop prion protein amyloid revealed by solid-state NMR spectroscopy. Nat. Comm. 8, 753 (2017).
3. Theint, T., Nadaud, P. S., Surewicz, K., Surewicz, W. K. and Jaroniec, C. P. 13C and 15N chemical shift assignments of mammalian Y145Stop prion protein amyloid fibrils. Biomol. NMR Assign. 11, 75-80 (2017).

Keywords: Prion, cross-seeding, solid-state NMR