Exploring the role of three α-helices on the structural conversion of mouse prion protein
Date Issued
2012
Date
2012
Author(s)
Luo, Wei-Lin
Abstract
Transmissible Spongiform Encephalopathies (TSE), also called prion diseases are infectious neurodegenerative disorders. The key molecular event in the pathogenesis of prion diseases is the conformational conversion of a cellular prion protein, PrPC, into a misfolded form, PrPSc. The α to β conformational transition leads to protein aggregation and the formation of toxic amyloid fibrils. However, the mechanism of protein misfolding and the pathogenic pathway are still unclear. In our lab’s previous study, we found that the disulfide-deleted mouse PrP could undergo a spontaneous structural conversion under native condition from the native α-helical structure to β-oligomers, amorphous aggregate, even amyloid fibrils. Here, we made spin-labeling on each of three helices of mouse prion protein individually and combined circular dichroism spectroscopy and electron spin resonance (ESR) spectroscopy to investigate the structural conversion process. Our study illustrated that helix 1 and helix 2 were partially unfolded when converted into soluble β-structures. On the other hand, spin labeled on helix 3 showed slow mobility, suggesting that the local environment of that spin is in an ordered state. Moreover, when the helix3-labeled protein was transformed into amyloid fibrils, the spin-labeled fibrils showed intermolecular spin interaction with a distance of 10 A.
Subjects
Prion disease
misfolding
structural conversion
Type
thesis
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