Prion diseases and the BSE crisis.
Prusiner SB
Department of Neurology, University of California, San Francisco, CA 94143, USA.
Bovine spongiform encephalopathy (BSE) and human Creutzfeldt-Jakob disease (CJD) are
among the most notable central nervous system degenerative disorders caused by prions. CJD
may present as a sporadic, genetic, or infectious illness. Prions are transmissible particles that are
devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrPSc). The
normal, cellular prion protein (PrPC) is converted into PrPSc through a posttranslational process
during which it acquires a high beta-sheet content. It is thought that BSE is a result of
cannibalism in which faulty industrial practices produced prion-contaminated feed for cattle.
There is now considerable concern that bovine prions may have been passed to humans,
resulting in a new form of CJD.
There are
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NMR structure of the mouse prion protein domain
PrP(121-321).
Riek R, Hornemann S, Wider G, Billeter M, Glockshuber R, Wuthrich K
Institut fur Molekularbiologie und Biophysik, Eidgenossische Technische
Hochschule-Honggerberg, Zurich, Switzerland.
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. Knowledge of
the three-dimensional structure of PrPc is essential for understanding the transition to PrPsc. The
nuclear magnetic resonance (NMR) structure of the autonomously folding PrP domain
comprising residues 121-231 (ref. 6) contains a two-stranded antiparallel beta-sheet and three
alpha-helices. This domain contains most of the point-mutation sites that have been linked, in
human PrP, to the occurrence of familial prion diseases. The NMR structure shows that these
mutations occur within, or directly adjacent to, regular secondary structures. The presence of a
beta-sheet in PrP(121-231) is in contrast with model predictions of an all-helical structure of
PrPc (ref. 8), and may be important for the initiation of the transition from PrPc to PrPsc.