title: A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform.
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.
authors.affiliation: Department of Neurology, School of Pharmacy, University of California, San Francisco, CA 94143, USA.
authors.forename: D
authors.initials: D
authors.lastname: Peretz
authors.forename: R A
authors.initials: RA
authors.lastname: Williamson
authors.forename: Y
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: H
authors.initials: H
authors.lastname: Serban
authors.forename: C
authors.initials: C
authors.lastname: Pinilla
authors.forename: R B
authors.initials: RB
authors.lastname: Bastidas
authors.forename: R
authors.initials: R
authors.lastname: Rozenshteyn
authors.forename: T L
authors.initials: TL
authors.lastname: James
authors.forename: R A
authors.initials: RA
authors.lastname: Houghten
authors.forename: F E
authors.initials: FE
authors.lastname: Cohen
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: D R
authors.initials: DR
authors.lastname: Burton
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006146:Guanidines / Q000494:pharmacology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007536:Isomerism; D008647:Mesocricetus; D051379:Mice; D008958:Models, Molecular; D018622:PrP 27-30 Protein / Q000138:chemical synthesis / Q000737:chemistry* / Q000187:drug effects / Q000276:immunology; D018621:PrPC Proteins / Q000737:chemistry* / Q000276:immunology; D011233:Precipitin Tests; D011487:Protein Conformation; D011489:Protein Denaturation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology; D012608:Scrapie / Q000276:immunology; D013329:Structure-Activity Relationship; D013861:Thiocyanates / Q000494:pharmacology
chemical_list: D018985:Epitopes, B-Lymphocyte; D006146:Guanidines; D007140:Immunoglobulin Fab Fragments; D018621:PrPC Proteins; D011993:Recombinant Fusion Proteins; D013861:Thiocyanates; D018622:PrP 27-30 Protein; C054436:guanidine thiocyanate