NR AJIY
AU Peretz,D.; Williamson,R.A.; Matsunaga,Y.; Serban,H.; Pinilla,C.; Bastidas,R.B.; Rozenshteyn,R.; James,T.L.; Houghten,R.A.; Cohen,F.E.; Prusiner,S.B.; Burton,D.R.
TI A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform
QU Journal of Molecular Biology 1997 Oct 31; 273(3): 614-22
PT journal article
AB The scrapie prion protein (PrPsc) is formed from the cellular isoform (PrPc) by a post-translational process that involves a profound conformational change. Linear epitopes for recombinant antibody Fab fragments (Fabs) on PrPc and on the protease-resistant core of PrPsc, designated PrP 27-30, were identified using ELISA and immunoprecipitation. An epitope region at the C terminus was accessible in both PrPc and PrP 27-30; in contrast, epitopes towards the N-terminal region (residues 90 to 120) were accessible in PrPc but largely cryptic in PrP 27-30. Denaturation of PrP 27-30 exposed the epitopes of the N-terminal domain. We argue from our findings that the major conformational change underlying PrPsc formation occurs within the N-terminal segment of PrP 27-30.
MH Animal; CHO Cells; Enzyme-Linked Immunosorbent Assay; Epitopes, B-Lymphocyte/chemistry/immunology; Guanidines/pharmacology; Hamsters; Immunoglobulins, Fab/immunology; Isomerism; Mesocricetus; Mice; Models, Molecular; PrP 27-30 Protein/chemical synthesis/*chemistry/drug effects/immunology; PrPc Proteins/*chemistry/immunology; Precipitin Tests; *Protein Conformation; Protein Denaturation; Recombinant Fusion Proteins/chemistry/immunology; *Scrapie/immunology; Structure-Activity Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thiocyanates/pharmacology
AD Department of Neurology, School of Pharmacy, University of California, San Francisco, CA 94143, USA
SP englisch
PO England