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Differential stability of the bovine prion protein upon urea unfolding
Author(s) -
Julien Olivier,
Chatterjee Subhrangsu,
Thiessen Angela,
Graether Steffen P.,
Sykes Brian D.
Publication year - 2009
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.231
Subject(s) - prion protein , chemistry , urea , protein stability , differential (mechanical device) , protein folding , prion proteins , biochemistry , biophysics , biology , physics , medicine , thermodynamics , disease , pathology
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, PrP C ; and the misfolded, infectious, and proteinase K‐resistant form, PrP Sc . The C‐terminal domain of PrP C is mainly α‐helical in structure, whereas PrP Sc in known to aggregate into an assembly of β‐sheets, forming amyloid fibrils. To identify the regions of PrP C 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 PrP C (residues 121 to 230) during unfolding with the denaturant urea. Analysis of the 800 MHz 1 H 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 PrP C 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.