Open Access13C and 15N chemical shift assignments of A117V and M129V human Y145Stop prion protein amyloid fibrils
Author(s) -
Hanh H. Dao,
May Z Hlaing,
Youjie Ma,
Krystyna Surewicz,
Witold K. Surewicz,
Christopher P. Jaroniec
Publication year - 2020
Publication title -
biomolecular nmr assignments
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.359
H-Index - 16
eISSN - 1874-2718
pISSN - 1874-270X
DOI - 10.1007/s12104-020-09981-4
Subject(s) - fibril , amyloid (mycology) , chemical shift , prion protein , chemistry , context (archaeology) , magic angle spinning , monomer , amyloid fibril , mutant , biophysics , in vitro , amyloid disease , amino acid , in vivo , prion proteins , biochemistry , nuclear magnetic resonance spectroscopy , amyloid β , biology , stereochemistry , genetics , disease , gene , medicine , organic chemistry , inorganic chemistry , paleontology , pathology , polymer
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 13 C and 15 N 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.