PrP N-terminal domain triggers PrP{sup Sc}-like aggregation of Dpl

Journal Article · Fri Jan 18 04:00:00 EST 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.10.202· OSTI ID:21043578

Erlich, Paul ^[1]; Cesbron, Jean-Yves ^[1]; Lemaire-Vieille, Catherine; Curt, Aurelie ^[1]; Andrieu, Jean-Pierre ^[2]; Schoehn, Guy; Jamin, Marc ^[3]; Gagnon, Jean ^[1]

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1. Laboratoire Adaptation et Pathogenie des Micro-organismes, Universite Joseph Fourier, BP 170, 38042 Grenoble Cedex 9 (France)
2. Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1 (France)
3. Unit of Virus Host Cell Interaction, UMR 5233 UJF-EMBL-CNRS, Carl-Ivar Braenden Building, 6 rue Jules Horowitz, BP 181, 38042 Grenoble Cedex (France)

Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP{sup C}, for 'cellular prion protein') into an abnormal state (PrP{sup Sc}, for 'scrapie prion protein'). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP{sup C}. In contrast to its homologue PrP{sup C}, Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP{sup Sc}-like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP{sup 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.

• OSTI ID: 21043578
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 365; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AGGLOMERATION
ELECTRON MICROSCOPY
GLYCOPROTEINS
IN VITRO
MICE
PEPSIN
PROTEOLYSIS
RESIDUES
SODIUM CHLORIDES