A Conformational Transition at the N Terminus of the Prion Protein Features in Formation of the Scrapie Isoform

J Mol Biol. 1997 Oct 31;273(3):614-22. doi: 10.1006/jmbi.1997.1328.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • 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
  • Precipitin Tests
  • Protein Conformation*
  • Protein Denaturation
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / immunology
  • Scrapie* / immunology
  • Structure-Activity Relationship
  • Thiocyanates / pharmacology

Substances

  • Epitopes, B-Lymphocyte
  • Guanidines
  • Immunoglobulin Fab Fragments
  • PrPC Proteins
  • Recombinant Fusion Proteins
  • Thiocyanates
  • PrP 27-30 Protein
  • guanidine thiocyanate