A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform

• Published in: Journal of molecular biology Vol. 273; no. 3; pp. 614 - 622
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England 31.10.1997
• Subjects: Animals; CHO Cells; Cricetinae; Enzyme-Linked Immunosorbent Assay; Epitopes, B-Lymphocyte - chemistry; Epitopes, B-Lymphocyte - immunology; Guanidines - pharmacology; Immunoglobulin Fab Fragments - immunology; Isomerism; Mesocricetus; Mice; Models, Molecular; Precipitin Tests; Protein Conformation; Protein Denaturation; PrP 27-30 Protein - chemical synthesis; PrP 27-30 Protein - chemistry; PrP 27-30 Protein - drug effects; PrP 27-30 Protein - immunology; PrPC Proteins - chemistry; PrPC Proteins - immunology; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - immunology; Scrapie - immunology; Structure-Activity Relationship; Thiocyanates - pharmacology
• ISSN: 0022-2836
• DOI: 10.1006/jmbi.1997.1328

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.