Transmissible spongiform encephalopathies (TSEs) are prion protein misfolding diseases that involve the accumulation
of an abnormal β-sheet-rich prion protein aggregated form (PrPsc) of the normal α- helix-rich prion protein
(PrPc) within the central nervous system (CNS) and other organs. On account of its large size and insolubility properties,
characterization of PrPc is quite difficult. A soluble intermediate, called PrPβ or βo, exhibiting many of the same features
as PrPsc, can be generated using a combination of low pH and/or mild denaturing conditions. Here, we review the current
knowledge on the following five issues relevant to the conversion mechanisms of PrPc to PrPsc : (1) How is the Stability of
the Helical Structures in the Native PrPc Related to the Primary Structure of the PrPc (2) Why the Low pH Solution System
is a Ideal Trigger of PrPc to PrPsc Conversion (3) How are the Structural and Dynamical Characteristics of the α-helixrich
Intermediates Determined using NMR Data (4) How are the Premolten (PrPα4 and PrPαβ) and β-Oligomer (PrPβ) Intermediates
Detected and Assayed, and (5) Can the Disordered N-terminal Domain be folded into the Structural Segment?
Particularly, Chou’s wenxiang diagram (http://en.wikipedia.org/wiki/Wenxiang_diagram) was introduced for providing an
intuitive picture. This review may help to further understand the prion protein misfolding mechanism.
Keywords: PrP, protein misfolding, NMR spectroscopy, CD, β-oligomer, premolten globule state, salt-bridge network, Chou’s
Rights & PermissionsPrintExport