Differential stability of the bovine prion protein upon urea unfolding
Open Access
- 23 September 2009
- journal article
- research article
- Published by Wiley in Protein Science
- Vol. 18 (10), 2172-2182
- https://doi.org/10.1002/pro.231
Abstract
Prion diseases, or transmissible spongiform encephalopathies, are a group of infectious neurological diseases associated with the structural conversion of an endogenous protein (PrP) in the central nervous system. There are two major forms of this protein: the native and noninfectious cellular form, PrPC; and the misfolded, infectious, and proteinase K‐resistant form, PrPSc. The C‐terminal domain of PrPC is mainly α‐helical in structure, whereas PrPSc in known to aggregate into an assembly of β‐sheets, forming amyloid fibrils. To identify the regions of PrPC potentially involved in the initial steps of the conversion to the infectious conformation, we have used high‐resolution NMR spectroscopy to characterize the stability and structure of bovine recombinant PrPC (residues 121 to 230) during unfolding with the denaturant urea. Analysis of the 800 MHz 1H NMR spectra reveals region‐specific information about the structural changes occurring upon unfolding. Our data suggest that the dissociation of the native β‐sheet of PrPC is a primary step in the urea‐induced unfolding process, while strong hydrophobic interactions between helices α1 and α3, and between α2 and α3, stabilize these regions even at very high concentrations of urea.Keywords
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