NR AASK
AU Apetri,A.C.; Surewicz,W.K.
TI Kinetic intermediate in the folding of human prion protein
QU The Journal of Biological Chemistry 2002 Nov 22; 277(47): 44589-92
IA http://www.jbc.org/cgi/content/full/277/47/44589
PT journal article
AB Transmissible spongiform encephalopathies are associated with the conversion of cellular prion protein, PrPc, into a misfolded oligomeric form, PrPsc. Here we have examined the kinetics of folding and unfolding reactions for the recombinant human prion protein C-terminal fragment 90-231 at pH 4.8 and 7.0. The stopped-flow data provide clear evidence for the population of an intermediate on the refolding pathway of the prion protein as indicated by a pronounced curvature in chevron plots and the presence of significant burst phase amplitude in the refolding kinetics. In addition to its role in the normal prion protein folding, this intermediate likely represents a crucial monomeric precursor of the pathogenic PrPsc isoform.
MH Humans; Hydrogen-Ion Concentration; Kinetics; Mutagenesis, Site-Directed; Peptide Fragments/*chemistry/genetics/*metabolism; Prion Diseases/genetics/physiopathology; Prions/*chemistry/genetics/*metabolism; Protein Denaturation; *Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins/chemistry/genetics/metabolism; Research Support, U.S. Gov't, P.H.S.
AD Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, USA
SP englisch
PO USA