tailieunhanh - Báo cáo khoa học: Copper-dependent degradation of recombinant ovine prion protein Phosphatidylinositol stimulates aggregation and copper-driven disappearance of prion protein

Prion protein (PrP) plays an important role in cell protection from oxida-tive stress due to its action as copper-chelating protein. The present study demonstrates that PrP participates in reductions of Cu 2+ to Cu + ions, and that this process results in fragmentation of protein. | ềFEBS Journal Copper-dependent degradation of recombinant ovine prion protein Phosphatidylinositol stimulates aggregation and copper-driven disappearance of prion protein Kirill Tsiroulnikov Jean-Marc Chobert and Thomas Haertle FIPL BIA Institut Nationalde la Recherche Agronomique Nantes France Keywords copper phosphatidylinositol prion protein Correspondence T. Haertle FIPL BIA Institut Nationalde la Recherche Agronomique . 71627 F-44316 Nantes Cedex 3 France Fax 33 2 40675244 Tel 33 2 40675091 E-mail haertle@ On leave from the Laboratory of Proteolytic Enzyme Chemistry Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of RAS Moscow Russia Received 21 December 2005 revised 24 February 2006 accepted 2 March 2006 Prion protein PrP plays an important role in cell protection from oxidative stress due to its action as copper-chelating protein. The present study demonstrates that PrP participates in reductions of Cu2 to Cu ions and that this process results in fragmentation of protein. The interaction with phosphatidylinositol a natural phospholipid moiety bound to PrP strongly enhances recombinant PrP aggregation and degradation. The copperdependent PrP degradation could promote the formation of amyloid structures destabilizing the PrP soluble form by the cleavage of the N-terminal part. doi Transformation of normal physiological form of prion protein PrPC into its pathogenic amyloid isoforms PrPSc is the main cause of degenerative disorders of the nervous system such as transmissible spongiform encephalopathies. The best known types of transmissible spongiform encephalopathy TSE are human Creutzfeldt-Jakob disease ovine scrapie and bovine spongiform encephalopathy. PrPC fi PrPSc transformation implies transition of monomeric a-helical protein into a b-sheeted fibrillar structure strongly resistant to proteolysis 1 . This transition is autocatalytic catalyzed by PrPSc itself and the principal role in this .