PrP N-terminal domain triggers PrP(Sc)-like aggregation of Dpl.
Biochem Biophys Res Commun
; 365(3): 478-83, 2008 Jan 18.
Article
em En
| MEDLINE
| ID: mdl-17997980
ABSTRACT
Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP(C), for "cellular prion protein") into an abnormal state (PrP(Sc), for "scrapie prion protein"). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP(C). In contrast to its homologue PrP(C), Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP(Sc)-like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP(C) (residues 23-125) and the C-terminal part of Dpl (residues 58-157). This chimeric protein displays PrP-like biochemical and structural features; when incubated in presence of NaCl, the alpha-helical monomer forms soluble beta-sheet-rich oligomers which acquire partial resistance to pepsin proteolysis in vitro, as do PrP oligomers. Moreover, the presence of aggregates akin to protofibrils is observed in soluble oligomeric species by electron microscopy.
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Príons
/
Proteínas PrPC
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article