Abstract
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 13C and 15N 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–Straüssler–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.
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Acknowledgements
This research was supported by NIH (Grants R01GM094357 and S10OD012303 to C.P.J., P01AI106705 and R01NS083687 to W.K.S., and RF1AG061797 to W.K.S. and C.P.J.), and NSF (Grant MCB-1715174 to C.P.J.).
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Chemical shift assignments for A117V and M129V huPrP23-144 amyloid fibrils have been deposited in the BioMagResBank (https://www.bmrb.wisc.edu) under accession numbers 50,312 and 50,313, respectively.
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Dao, H.H., Hlaing, M.Z., Ma, Y. et al. 13C and 15N chemical shift assignments of A117V and M129V human Y145Stop prion protein amyloid fibrils. Biomol NMR Assign 15, 45–51 (2021). https://doi.org/10.1007/s12104-020-09981-4
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DOI: https://doi.org/10.1007/s12104-020-09981-4