NR AFXO
AU Jackson,G.S.; Hosszu,L.L.P.; Power,A.; Hill,A.F.; Kenney,J.; Saibil,H.; Craven,C.J.; Waltho,J.P.; Clarke,A.R.; Collinge,J.
TI Reversible conversion of monomeric human prion protein between native and fibrilogenic conformations
QU Science 1999 Mar 19; 283(5409): 1935-7
PT journal article
AB Prion propagation involves the conversion of cellular prion protein (PrPc) into a disease-specific isomer, PrPsc, shifting from a predominantly alpha-helical to beta-sheet structure. Here, conditions were established in which recombinant human PrP could switch between the native alpha conformation, characteristic of PrPc, and a compact, highly soluble, monomeric form rich in beta structure. The soluble beta form (beta-PrP) exhibited partial resistance to proteinase K digestion, characteristic of PrPsc, and was a direct precursor of fibrillar structures closely similar to those isolated from diseased brains. The conversion of PrPc to beta-PrP in suitable cellular compartments, and its subsequent stabilization by intermolecular association, provide a molecular mechanism for prion propagation.
ZR 23 Zitate
MH Circular Dichroism; Endopeptidase K/metabolism; Human; Hydrogen-Ion Concentration; Molecular Weight; Nuclear Magnetic Resonance, Biomolecular; Oxidation-Reduction; PrPc Proteins/chemistry; PrPsc Proteins/chemistry; Prions/*chemistry; *Protein Conformation; Protein Folding; Protein Isoforms/chemistry; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins/chemistry; Solubility; Spectrum Analysis; Support, Non-U.S. Gov't
AD Prion Disease Group, Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1NY, UK
SP englisch
PO USA