NR ABAY
AU Baskakov,I.V.; Legname,G.; Prusiner,S.B.; Cohen,F.E.
TI Folding of prion protein to its native alpha-helical conformation is under kinetic control
QU The Journal of Biological Chemistry 2001 Jun 8; 276(23): 19687-90
IA http://www.jbc.org/cgi/content/full/276/23/19687
PT journal article
AB 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.
MH Circular Dichroism; Kinetics; Prions/*chemistry; Protein Conformation; Protein Folding; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Thermodynamics
AD Institute for Neurodegenerative Diseases, Department of Neurology, University of California, San Francisco, California 94143, USA
SP englisch
PO USA