Proteolytic fragmentation of the murine prion protein: role of Tyr‐128 and His‐177

FEBS Letters

Perera, W.Sumudhu S¹  Hooper, Nigel M¹ 

[1] School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK

关键词: Transmissible spongiform encephalopathy;    Proteolysis;    Glycosyl-phosphatidylinositol anchor;    Serine protease;    Signal peptidase;    DIG;    detergent-insoluble;    cholesterol- and glycosphingolipid-rich membrane domain;    GPI;    glycosyl-phosphatidylinositol;    MBS;    MES-buffered saline;    PI-PLC;    phosphatidylinositol-specific phospholipase C;    PNGase F;    peptide N-glycosidase F;    PrP;    prion protein;    PrPC;    normal cellular form of PrP;    PrPSc;    scrapie isoform of PrP;    PVDF;    poly(vinylidene difluoride);   

DOI  :  10.1016/S0014-5793(99)01648-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The prion protein (PrP) has been proposed to display sequence and structural similarities to membrane-anchored signal peptidases [Glockshuber et al. (1998) FEBS Lett. 426, 291–296]. We have investigated the role of Tyr-128 and His-177 in the proteolytic fragmentation of murine PrP by mutating these residues to Phe and Leu, respectively, and expressing the resultant mutants in the human neuroblastoma SH-SY5Y. Both PrP-Y128F and PrP-H177L were expressed at the cell surface as glycosyl-phosphatidylinositol-anchored forms and were localised in detergent-insoluble membrane domains similar to wild type PrP. Following deglycosylation, the 19 kDa proteolytic fragment PrP-II was present in cells expressing either mutant, indicating that Tyr-128 and His-177 are not involved in the proteolytic fragmentation of PrP.

【 授权许可】

Unknown