Document Detail


Truncated forms of the human prion protein in normal brain and in prion diseases.
MedLine Citation:
PMID:  7642585     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cellular form of the prion protein (PrPc) is a glycoprotein anchored to the cell membrane by a glycosylphosphatidylinositol moiety. An aberrant form of PrPc that is partially resistant to proteases, PrPres, is a hallmark of prion diseases, which in humans include Cruetzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. We have characterized the major forms of PrP in normal and pathological human brains. A COOH-terminal fragment of PrPc, designated C1, is abundant in normal and CJD brains as well as in human neuroblastoma cells. Sequence analysis revealed that C1 contains alternative NH2 termini starting at His-111 or Met-112. Like PrPc, C1 is glycosylated, anchored to the cell membrane, and is heat-stable. Consistent with the lack of the NH2-terminal region of PrPc, C1 is more acidic than PrPc and does not bind heparin. An additional fragment longer than C1, designated C2, is present in substantial amounts in CJD brains. Like PrPres, C2 is resistant to proteases and is detergent-insoluble. Our data indicate that C1 is a major product of normal PrPc metabolism, generated by a cleavage that disrupts the neurotoxic and amyloidogenic region of PrP comprising residues 106-126. This region remains intact in C2, suggesting a role for C2 in prion diseases.
Authors:
S G Chen; D B Teplow; P Parchi; J K Teller; P Gambetti; L Autilio-Gambetti
Related Documents :
19616765 - Responses to amyloids of microbial and host origin are mediated through toll-like recep...
19640715 - A chemical screening approach reveals that indole fluorescence is quenched by pre-fibri...
17295405 - Spider silk and amyloid fibrils: a structural comparison.
12525175 - Probing the role of backbone hydrogen bonding in beta-amyloid fibrils with inhibitor pe...
20458515 - Myoinhibiting peptides are the ancestral ligands of the promiscuous drosophila sex pept...
20682285 - Crystal structures of two archaeal pelotas reveal inter-domain structural plasticity.
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  270     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-09-18     Completed Date:  1995-09-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  19173-80     Citation Subset:  IM    
Affiliation:
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Amino Acid Sequence
Brain Chemistry*
Humans
Middle Aged
Molecular Sequence Data
Neuroblastoma / chemistry
Peptide Fragments / analysis
Prion Diseases / metabolism*
Prions / analysis*,  chemistry
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
AG08155/AG/NIA NIH HHS; AG08992/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Peptide Fragments; 0/Prions

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Identification of the major phosphorylation sites in human C5a anaphylatoxin receptor in vivo.
Next Document:  Irradiation induces WAF1 expression through a p53-independent pathway in KG-1 cells.