The recombinant mouse prion protein (MoPrP) can be folded either to a monomeric alpha-helical or oligomeric beta-sheet-rich isoform. By using circular dichroism spectroscopy and size-exclusion chromatography, we show that the beta-rich isoform of MoPrP is thermodynamically more stable than the native alpha-helical isoform. The conformational transition from the alpha-helical to beta-rich isoform is separated by a large energetic barrier that is associated with unfolding and with a higher order kinetic process related to oligomerization. Under partially denaturing acidic conditions, MoPrP avoids the kinetic trap posed by the alpha-helical isoform and folds directly to the thermodynamically more stable beta-rich isoform. Our data demonstrate that the folding of the prion protein to its native alpha-helical monomeric conformation is under kinetic control.
|Titolo:||Folding of prion protein to its native α-helical conformation is under kinetic control|
|Autori:||Baskakov, I. V.; Legname, G.; Prusiner, S. B.; Cohen, F. E.|
|Data di pubblicazione:||2001|
|Digital Object Identifier (DOI):||10.1074/jbc.C100180200|
|Appare nelle tipologie:||1.1 Journal article|