title: The binding of prion proteins to serum components is affected by detergent extraction conditions.
abstract: As many GPI anchored proteins, PrP(C) and its abnormal conformer PrP(Sc), are inserted into membrane microdomains known as rafts. Upon raft disruption, PrP(C) becomes soluble, while PrP(Sc) aggregates into insoluble structures. It was recently published that, as opposed to PrP(C), PrP(Sc), as well as its protease resistant core PrP27-30, can bind specifically to plasminogen and other serum components. These findings were suggested to have important physiological implications in transmissible spongiform encephalopathies (TSE) diagnosis and pathogenesis. In this work, we show that the binding of PrP(Sc) or PrP 27-30 to serum proteins occurs only at specific detergent combinations, in which disease associated PrPs are present in aggregated structures. At detergent conditions in which rafts are intact, it is actually PrP(C.) that binds to blood proteins, albeit not directly, but through neighboring rafts components. Our results therefore indicate that the binding of PrP(Sc) to blood components has no physiological relevance.
authors.affiliation: Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel 91120.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Shaked
authors.forename: Roni
authors.initials: R
authors.lastname: Engelstein
authors.forename: Ruth
authors.initials: R
authors.lastname: Gabizon
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000737:chemistry*; D001923:Brain Chemistry; D003902:Detergents / Q000737:chemistry* / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D015151:Immunoblotting; D046911:Macromolecular Substances; D008280:Magnetics; D021962:Membrane Microdomains / Q000737:chemistry; D051379:Mice; D010958:Plasminogen / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D012995:Solubility / Q000187:drug effects
chemical_list: D001798:Blood Proteins; D003902:Detergents; D046911:Macromolecular Substances; D011328:Prions; D010958:Plasminogen; D006493:Heparin