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Sequence-dependent prion protein misfolding and neurotoxicity.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2010 Nov 19; Vol. 285 (47), pp. 36897-908. Date of Electronic Publication: 2010 Sep 03. - Publication Year :
- 2010
-
Abstract
- Prion diseases are neurodegenerative disorders caused by misfolding of the normal prion protein (PrP) into a pathogenic "scrapie" conformation. To better understand the cellular and molecular mechanisms that govern the conformational changes (conversion) of PrP, we compared the dynamics of PrP from mammals susceptible (hamster and mouse) and resistant (rabbit) to prion diseases in transgenic flies. We recently showed that hamster PrP induces spongiform degeneration and accumulates into highly aggregated, scrapie-like conformers in transgenic flies. We show now that rabbit PrP does not induce spongiform degeneration and does not convert into scrapie-like conformers. Surprisingly, mouse PrP induces weak neurodegeneration and accumulates small amounts of scrapie-like conformers. Thus, the expression of three highly conserved mammalian prion proteins in transgenic flies uncovered prominent differences in their conformational dynamics. How these properties are encoded in the amino acid sequence remains to be elucidated.
- Subjects :
- Amino Acid Sequence
Animals
Animals, Genetically Modified
Blotting, Western
Chromatography, Gel
Conserved Sequence
Cricetinae
Drosophila melanogaster growth & development
Drosophila melanogaster metabolism
Female
Fluorescent Antibody Technique
Immunoprecipitation
Locomotion physiology
Male
Mice
Molecular Sequence Data
Neurotoxicity Syndromes metabolism
Neurotoxicity Syndromes pathology
Prion Diseases genetics
Prion Diseases metabolism
Prions metabolism
Protein Conformation
RNA, Messenger genetics
Rabbits
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Drosophila melanogaster genetics
Neurotoxicity Syndromes etiology
Prion Diseases pathology
Prions chemistry
Prions genetics
Protein Folding
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 285
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20817727
- Full Text :
- https://doi.org/10.1074/jbc.M110.174391