Prion protein structural features indicate possible relations to signal peptidases

FEBS Letters

Riek, Roland¹  Wider, Gerhard¹  Billeter, Martin¹  Glockshuber, Rudi¹  Hornemann, Simone¹  Wüthrich, Kurt¹ 

[1] Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule-Hönggerberg, CH-8093 Zürich, Switzerland

关键词: Transmissible spongiform encephalopathy;    Cellular prion protein;    Signal peptidase;    Three-dimensional structure;    Sequence similarity;   

DOI  :  10.1016/S0014-5793(98)00372-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 α-helices and a two-stranded β-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).

【 授权许可】

Unknown