Nature 1996 Jul 11;382(6587):180-2

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.

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