13C and 15N chemical shift assignments of A117V and M129V human Y145Stop prion protein amyloid fibrils

The C-terminally truncated Y145Stop variant of prion protein (PrP23-144) has been linked to a heritable prionopathy in humans and is also capable of triggering a transmissible prion disease in mice. PrP23-144 can be converted from soluble monomeric form to amyloid under physiological conditions, providing an in vitro model for investigating the molecular basis of amyloid strains and cross-seeding barriers. Here, we use magic-angle spinning solid-state NMR to establish the sequential backbone and sidechain C-13 and N-15 chemical shift assignments for amyloid fibrils formed by the A117V and M129V mutants of human PrP23-144, which in the context of full length PrP in vivo are among the specific residues associated with development of Gerstmann-Straussler-Scheinker disease. The chemical shift data are utilized to identify amino acids comprising the rigid amyloid core regions and to predict the protein secondary structures for human PrP23-144 A117V and M129V fibrils.

Automated summary

Solid-state NMR was used to establish the chemical shift assignments for amyloid fibrils formed by the A117V and M129V mutants of human PrP23-144, providing insights into the amyloid core regions and secondary protein structures. These mutants are associated with the development of Gerstmann-Straussler-Scheinker disease in the context of full-length PrP in vivo.