pH-dependent stability and conformation of the recombinant human prion protein PrP(90-231)

Wieslaw Swietnicki, Robert Petersen, Pierluigi Gambetti, Witold K. Surewicz

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A recombinant protein corresponding to the human prion protein domain encompassing residues 90-231 (huPrP(90-231)) was expressed in Escherichia coli in a soluble form and purified to homogeneity. Spectroscopic data indicate that the conformational properties and the folding pathway of huPrP(90-231) are strongly pH-dependent. Acidic pH induces a dramatic increase in the exposure of hydrophobic patches on the surface of the protein. At pH between 7 and 5, the unfolding of hPrP(90-231) in guanidine hydrochloride occurs as a two-state transition. This contrasts with the unfolding curves at lower pH values, which indicate a three-state transition, with the presence of a stable protein folding intermediate. While the secondary structure of the native huPrP(90-231) is largely α-helical, the stable intermediate is rich in β-sheet structure. These findings have important implications for understanding the initial events on the pathway toward the conversion of the normal into the pathological forms of prion protein.

Original languageEnglish
Pages (from-to)27517-27520
Number of pages4
JournalJournal of Biological Chemistry
Issue number44
StatePublished - Oct 31 1997


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