Published erratum appears in FEBS Lett 1998 Jul 10;431(1):130

Prion protein structural features indicate possible relations to
signal peptidases.

Glockshuber R, Hornemann S, Billeter M, Riek R, Wider G, Wuthrich K

Institut fur Molekularbiologie und Biophysik, Eidgenossische Technische Hochschule-Honggerberg,
Zurich, Switzerland. RUDI@MOL.BIOL.ETHZ.CH

Transmissible spongiform encephalopathies (TSEs) in mammalian species are believed to be caused by
an oligomeric isoform, PrP(Sc), of the cellular prion protein, PrP(C). One of the key questions in TSE
research is how the observed accumulation of PrP(Sc), or possibly the concomitant depletion of PrP(C)
can cause fatal brain damage. Elucidation of the so far unknown function of PrP(C) is therefore of
crucial importance. PrP(C) is a membrane-anchored cell surface protein that possesses a so far unique
three-dimensional structure. While the N-terminal segment 23-120 of PrP(C) is flexibly disordered,
its C-terminal residues 121-231 form a globular domain with three alpha-helices and a two-stranded
beta-sheet. Here we report the observation of structural similarities between the domain of
PrP(121-231) and the soluble domains of membrane-anchored signal peptidases. At the level of the
primary structure we find 23% identity and 41% similarity between residues 121-217 of the
C-terminal domain of murine PrP and a catalytic domain of the rat signal peptidase. The invariant PrP
residues Tyr-128 and His-177 align with the two presumed active-site residues of signal peptidases
and are in close spatial proximity in the three-dimensional structure of PrP(121-231).

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