Biochemistry · 2002 · 157 citations · 5 references
Life SciencesBiochemistryMolecular BiologyProtein BiochemistryProtein FoldingStructural BiologyFolding IntermediatesIntrinsically Disordered ProteinsPrion Protein MisfoldingPrion Protein StructureProtein ConformationProtein StructureCellular Prion Protein StructureConformational Conversion MechanismsPh DependencePrion Conformational ConversionPrion Conversion MechanismPrion Protein ConformationPrion Protein FoldingTwo-dimensional Nmr Spectroscopy
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.
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High pressure NMR reveals a variety of fluctuating conformers in β-lactoglobulin
Kazuo Kuwata, Hua Li, Hiroaki Yamada et al. · Journal of Molecular Biology · 2001 · 81 citations