A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform.
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.
Peretz
D
D
Department of Neurology, School of Pharmacy, University of California, San Francisco, CA 94143, USA.
Williamson
R A
RA
Matsunaga
Y
Y
Serban
H
H
Pinilla
C
C
Bastidas
R B
RB
Rozenshteyn
R
R
James
T L
TL
Houghten
R A
RA
Cohen
F E
FE
Prusiner
S B
SB
Burton
D R
DR
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
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