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The 'protein only' hypothesis states that a modified form of normal prion protein triggers infectious neurodegenerative diseases, such as bovine spongiform encephalopathy (BSE), or Creutzfeldt-Jakob disease (CJD) in humans. Prion proteins are thought to exist in two different conformations: the 'benign' PrPcform, and the infectious 'scrapie form', PrPsc.(More)
Prions are infectious particles causing transmissible spongiform encephalopathies (TSEs). They consist, at least in part, of an isoform (PrPSc) of the ubiquitous cellular prion protein (PrPC). Conformational differences between PrPC and PrPSc are evident from increased beta-sheet content and protease resistance in PrPSc. Here we describe a monoclonal(More)
The recombinant murine prion protein, mPrP(23-231), was expressed in E. coli with uniform 15N-labeling. NMR experiments showed that the previously determined globular three-dimensional structure of the C-terminal domain mPrP(121-231) is preserved in the intact protein, and that the N-terminal polypeptide segment 23-120 is flexibly disordered. This(More)
The cellular prion protein of the mouse, mPrP(C), consists of 208 amino acids (residues 23-231). It contains a carboxy-terminal domain, mPrP(121-231), which represents an autonomous folding unit with three alpha-helices and a two-stranded antiparallel beta-sheet. We expressed the complete amino acid sequence of the prion protein, mPrP(23-231), in the(More)
Most transmissible spongiform encephalopathies arise either spontaneously or by infection. Mutations of PRNP, which encodes the prion protein, PrP, segregate with phenotypically similar diseases. Here we report that moderate overexpression in transgenic mice of mPrP(170N,174T), a mouse PrP with two point mutations that subtly affect the structure of its(More)
The refined NMR structure of the mouse prion protein domain mPrP(121-231) and the recently reported NMR structure of the complete 208-residue polypeptide chain of mPrP are used to investigate the structural basis of inherited human transmissible spongiform encephalopathies. In the cellular form of mPrP no spatial clustering of mutation sites is observed(More)
By immunizing prion knockout mice (Prnp-/-) with recombinant murine prion protein (PrPc), we obtained a panel of mAbs specific for murine PrPc. These mAbs can be applied to immunoblotting, cell surface immunofluorescent staining, and immunohistochemistry at light and electron microscopy. These mAbs recognize both the normal (PrPc) and protease-resistant(More)
The infectious agent of transmissible spongiform encephalopathies is believed to consist of an oligomeric isoform, PrPSc, of the monomeric cellular prion protein, PrPC. The conversion of PrPC to PrPSc is characterized by a decrease in alpha-helical structure, an increase in beta-sheet content, and the formation of PrPSc amyloid. Whereas the N-terminal part(More)
The recent introduction of bank vole (Clethrionomys glareolus) as an additional laboratory animal for research on prion diseases revealed an important difference when compared to the mouse and the Syrian hamster, since bank voles show a high susceptibility to infection by brain homogenates from a wide range of diseased species such as sheep, goats, and(More)
NMR structures are presented for the recombinant construct of residues 121-230 from the tammar wallaby (Macropus eugenii) prion protein (PrP) twPrP(121-230) and for the variant mouse PrPs mPrP[Y225A,Y226A](121-231) and mPrP[V166A](121-231) at 20 degrees C and pH 4.5. All three proteins exhibit the same global architecture as seen in other recombinant(More)