NR AGXW
AU Kuwata,K.; Li,H.; Yamada,H.; Legname,G.; Prusiner,S.B.; Akasaka,K.; James,T.L.
TI Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrPsc?
QU Biochemistry 2002 Oct 15; 41(41): 12277-83
PT journal article
AB A crucial step for transformation of the normal cellular isoform of the prion protein (PrPc) to the infectious prion protein (PrPsc) is thought to entail a previously uncharacterized intermediate conformer, PrP*, which interacts with a template PrPsc molecule in the conversion process. By carrying out (15)N-(1)H two-dimensional NMR measurements under variable pressure on Syrian hamster prion protein rPrP(90-231), we found a metastable conformer of PrPc coexisting at a population of approximately 1% at pH 5.2 and 30 degrees C, in which helices B and C are preferentially disordered. While the identity is still unproven, this observed metastable conformer is most logically PrP* or a closely related precursor. The structural characteristics of this metastable conformer are consistent with available immunological and pathological information about the prion protein.
MH Animal; Cold; Hamsters; Mesocricetus; Nitrogen Isotopes; Nuclear Magnetic Resonance, Biomolecular; Peptide Fragments/chemistry/metabolism; PrPsc Proteins/*chemistry/*metabolism; Pressure; Protein Conformation; Protein Folding; Protein Structure, Secondary; Protons; Recombinant Proteins/chemistry/metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thermodynamics
AD Department of Biochemistry and Biophysics, School of Medicine, Gifu University, 40 Tsukasa-machi, Gifu 500-8705, Japan.
SP englisch
PO USA