NR ALHN
AU Swietnicki,W.; Petersen,R.; Gambetti,P.; Surewicz,W.K.
TI pH-dependent stability and conformation of the recombinant human prion protein PrP(90-231)
QU The Journal of Biological Chemistry 1997 Oct 31; 272(44): 27517-20
PT journal article
AB 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 alpha-helical, the stable intermediate is rich in beta-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.
MH Circular Dichroism; Human; Hydrogen-Ion Concentration; Prions/*chemistry; Protein Conformation; Recombinant Proteins/chemistry; Spectrophotometry, Ultraviolet; Thermodynamics
AD Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
SP englisch
PO USA