Solid-state NMR studies of the prion protein HI fragment

Content Provider	Semantic Scholar
Author	Heller, Jonathan Kolbert, Andrew C. Larsen, Russell Ernst, Matthias Bekker, Tatiana Md Baldwin, Michael Prusiner, Stanley B. Pines, Alexander Wemmer, David E.
Copyright Year	2002
Abstract	Conformational changes in the prion protein (PrP) seem to be responsible for prion diseases. We have used conformation-dependent chemical-shift measurements and rotational-resonance distance measurements to analyze the conformation of solid-state peptides lacking long-range order, corresponding to a region of PrP designated H I . This region is predicted to undergo a transformation of secondary structure in generating the infectious form of the protein. Solid-state NMR spectra of specifically '3C-enriched samples of HI, residues 109-122 (MKHMAGAAAAGAVV) of Syrian hamster PrP, have be n acquired under cross-polarization and magic-angle spinning conditions. Samples lyophilized from 50% acetonitrile/50% water show chemical shifts characteristic of a 0-sheet conformation in the region corresponding to residues 112-121, whereas samples lyophilized from hexafluoroisopropanol display shifts indicative of a-helical secondary structure in the region corresponding to residues 113-1 17. Complete conversion to the helical conformation was not observed and conversion from a-helix back to 0-sheet, as inferred from the solid-state NMR spectra, occurred when samples were exposed to water. Rotational-resonance experiments were performed on seven doubly I3C-labeled H1 samples dried from water. Measured distances suggest that the peptide is in an extended, possibly &strand, conformation. These results are consistent with the experimental observation that P r P can exist in different conformational states and with structural predictions based on biological data and theoretical modeling that suggest that HI may play a key role in the conformational transition involved in the development of prion diseases.
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Alternate Webpage(s)	https://pines.berkeley.edu/sites/default/files/publications/solid-state_nmr_studies_of_the_prion_protein_h1_fragment.pdf
Language	English
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Content Type	Text
Resource Type	Article