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 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 copper-dependent PrP degradation could promote the formation of amyloid structures, destabilizing the PrP soluble form by the cleavage of the N-terminal part.
Tsiroulnikov
Kirill
K
FIPL, BIA, Institut National de la Recherche Agronomique, Nantes, France.
Chobert
Jean-Marc
JM
Haertlé
Thomas
T
D000818:Animals; D003300:Copper / Q000737:chemistry* / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000494:pharmacology*; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012756:Sheep; D013997:Time Factors
D010716:Phosphatidylinositols; D011328:Prions; D011994:Recombinant Proteins; D003300:Copper