NR AJZT
AU Riek,R.; Wider,G.; Billeter,M.; Hornemann,S.; Glockshuber,R.; Wüthrich,K.
TI Prion protein NMR structure and familial human spongiform encephalopathies
QU Proceedings of the National Academy of Sciences of the United States of America 1998 Sep 29; 95(20): 11667-72
PT journal article
AB The refined NMR structure of the mouse prion protein domain mPrP(121-231) and the recently reported NMR structure of the complete 208-residue polypeptide chain of mPrP are used to investigate the structural basis of inherited human transmissible spongiform encephalopathies. In the cellular form of mPrP no spatial clustering of mutation sites is observed that would indicate the existence of disease-specific subdomains. A hydrogen bond between residues 128 and 178 provides a structural basis for the observed highly specific influence of a polymorphism in position 129 in human PrP on the disease phenotype that segregates with the mutation Asp-178-Asn. Overall, the NMR structure implies that only part of the disease-related amino acid replacements lead to reduced stability of the cellular form of PrP, indicating that subtle structural differences in the mutant proteins may affect intermolecular signaling in a variety of different ways.
MH Animal; Comparative Study; Human; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Mice; Models, Molecular; Peptide Fragments/chemistry/genetics; Point Mutation; Polymorphism (Genetics); PrPc Proteins/chemistry/genetics; Prion Diseases/genetics/*metabolism; Prions/*chemistry/genetics; Protein Conformation; Support, Non-U.S. Gov't; Thermodynamics
AD Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule-Honggerberg, CH-8093 Zürich, Switzerland.
SP englisch
PO USA