NONGENETIC PROPAGATION OF STRAIN-SPECIFIC PROPERTIES OF SCRAPIE PRION PROTEIN

被引:459
作者
BESSEN, RA [1 ]
KOCISKO, DA [1 ]
RAYMOND, GJ [1 ]
NANDAN, S [1 ]
LANSBURY, PT [1 ]
CAUGHEY, B [1 ]
机构
[1] MIT,DEPT CHEM,CAMBRIDGE,MA 02139
关键词
D O I
10.1038/375698a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
THE infectious agents causing scrapie and other transmissible spongiform encephalopathies have been postulated to consist solely of the protease-resistant form of prion protein (PrPSc)(1-6). One unprecedented requirement of the protein-only model is that the 'inheritance' of pathogen strain differences must be mediated by stable variations in PrPSc structure(2,7,8), rather than mutations in an agent-specific nucleic acid(9). Strain differences in PrPSc structure have been described for the hyper (HY) and drowsy (DY) strains of hamster transmissible mink encephalopathy (TME)(7,8), a a scrapie-like disease originating in mink. Although HY and DY PrPSc are both post-translationally derived from the precursor prion protein (PrPc) they are cleaved at different amino-terminal sites by proteinase K (ref. 8). Here we investigate whether this strain-specific property of PrPSc is transmitted to PrPc during formation of new PrPSc. PrPSc from the HY and DY TME strains converted the protease-sensitive PrPc into two distinct sets of protease-resistant PrP products in a cell-free system. These data provide evidence that self-propagation of PrPSc polymers with distinct three-dimensional structures could be the molecular basis of scrapie strains.
引用
收藏
页码:698 / 700
页数:3
相关论文
共 14 条
[1]   DISTINCT PRP PROPERTIES SUGGEST THE MOLECULAR-BASIS OF STRAIN VARIATION IN TRANSMISSIBLE MINK ENCEPHALOPATHY [J].
BESSEN, RA ;
MARSH, RF .
JOURNAL OF VIROLOGY, 1994, 68 (12) :7859-7868
[2]   IDENTIFICATION OF 2 BIOLOGICALLY DISTINCT STRAINS OF TRANSMISSIBLE MINK ENCEPHALOPATHY IN HAMSTERS [J].
BESSEN, RA ;
MARSH, RF .
JOURNAL OF GENERAL VIROLOGY, 1992, 73 :329-334
[3]   BIOCHEMICAL AND PHYSICAL-PROPERTIES OF THE PRION PROTEIN FROM 2 STRAINS OF THE TRANSMISSIBLE MINK ENCEPHALOPATHY AGENT [J].
BESSEN, RA ;
MARSH, RF .
JOURNAL OF VIROLOGY, 1992, 66 (04) :2096-2101
[4]  
BOLTON DC, 1988, CIBA F SYMP, V135, P164
[5]   THE NEW BIOLOGY OF SPONGIFORM ENCEPHALOPATHY - INFECTIOUS AMYLOIDOSES WITH A GENETIC TWIST [J].
BROWN, P ;
GOLDFARB, LG ;
GAJDUSEK, DC .
LANCET, 1991, 337 (8748) :1019-1022
[6]   BIOLOGICAL EVIDENCE THAT SCRAPIE AGENT HAS AN INDEPENDENT GENOME [J].
BRUCE, ME ;
DICKINSON, AG .
JOURNAL OF GENERAL VIROLOGY, 1987, 68 :79-89
[7]  
CASPAR DLD, 1980, BIOPHYS J, V32, P101
[8]   A KINETIC-MODEL FOR AMYLOID FORMATION IN THE PRION DISEASES - IMPORTANCE OF SEEDING [J].
COME, JH ;
FRASER, PE ;
LANSBURY, PT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (13) :5959-5963
[9]   SELF-REPLICATION AND SCRAPIE [J].
GRIFFITH, JS .
NATURE, 1967, 215 (5105) :1043-&
[10]   SEEDING ONE-DIMENSIONAL CRYSTALLIZATION OF AMYLOID - A PATHOGENIC MECHANISM IN ALZHEIMERS-DISEASE AND SCRAPIE [J].
JARRETT, JT ;
LANSBURY, PT .
CELL, 1993, 73 (06) :1055-1058