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The pH-Triggered Conversion of the PrPc to PrPsc

[ Vol. 13 , Issue. 10 ]


Guo-Ping Zhou and Ri-Bo Huang   Pages 1152 - 1163 ( 12 )


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 ( was introduced for providing an intuitive picture. This review may help to further understand the prion protein misfolding mechanism.


PrP, protein misfolding, NMR spectroscopy, CD, β-oligomer, premolten globule state, salt-bridge network, Chou’s wenxiang diagram.


Gordon Life Science Institute, 53 South Cottage Road, Belmont, MA 02478, USA.

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