Locally disordered conformer of the hamster prion protein: a crucial intermediate to PrPSc?
A crucial step for transformation of the normal cellular isoform of the prion protein (PrP(C)) to the infectious prion protein (PrP(Sc)) is thought to entail a previously uncharacterized intermediate conformer, PrP*, which interacts with a template PrP(Sc) 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 PrP(C) 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.
D000818:Animals; D003080:Cold Temperature; D006224:Cricetinae; D008647:Mesocricetus; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D018620:PrPSc Proteins / Q000737:chemistry* / Q000378:metabolism*; D011312:Pressure; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011522:Protons; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
D009587:Nitrogen Isotopes; D010446:Peptide Fragments; D018620:PrPSc Proteins; D011522:Protons; D011994:Recombinant Proteins