Conformational changes in the prion protein (PrP) seem to be responsib
le for prion diseases. We have used conformation-dependent chemical-sh
ift measurements and rotational-resonance distance measurements to ana
lyze the conformation of solid-state peptides lacking long-range order
, corresponding to a region of PrP designated H1. This region is predi
cted to undergo a transformation of secondary structure in generating
the infectious form of the protein. Solid-state NMR spectra of specifi
cally C-13-enrrched samples of H1, residues 109-122 (MKHMAGAAAAGAVV) o
f Syrian hamster PrP, have been acquired under cross-polarization and
magic-angle spinning conditions. Samples lyophilized from 50% acetonit
rile/50% water show chemical shifts characteristic of a beta-sheet con
formation in the region corresponding to residues 112-121, whereas sam
ples lyophilized from hexafluoroisopropanol display shifts indicative
of alpha-helical secondary structure in the region corresponding to re
sidues 113-117. Complete conversion to the helical conformation was no
t observed and conversion from alpha-helix back to beta-sheet, as infe
rred from the solid-state NMR spectra, occurred when samples were expo
sed to water. Rotational-resonance experiments were performed on seven
doubly C-13-labeled H1 samples dried from water. Measured distances s
uggest that the peptide is in an extended, possibly beta-strand, confo
rmation. These results are consistent with the experimental observatio
n that PrP can exist in different conformational states and with struc
tural predictions based on biological data and theoretical modeling th
at suggest that H1 may play a key role in the conformational transitio
n involved in the development of prion diseases.