Characterization of a complex formed between human plasminogen and recombinant sheep prion: pressure and thermal sensitivity of complex formation.
Scrapie is thought to be caused by one or more conformations of a proteinacious particle called a prion. The infectious form(s) is referred to as the scrapie form of the prion protein (PrPsc) whereas a benign form, the cellular conformer, is referred to as PrPC. The cellular conformation of the sheep prion protein formed a 1:1 complex with human plasminogen. The complex precipitated at 0 degrees C (Ksp = 17* 10(-12) M2). This precipitation reaction was sensitive to both temperature and pressure. When subjected to hydrostatic pressure the precipitate dissolved. At 25 degrees C the complex was soluble with a dissociation constant of about 10(-7) M as determined by isothermal titration calorimetry. Absorption, fluorescence and circular dichroism spectroscopy showed that neither protein, in the complex, underwent a detectable structural change so long as proteolytic inhibitors were present. In the absence of proteolytic inhibitors, plasminogen slowly cleaved the prion protein.
Kornblatt
J A
JA
Concordia University, Montreal, Qc, Canada. krnbltt@vax2.concordia.ca
Marchal
S
S
Rezaei
H
H
Balny
C
C
D000818:Animals; D002151:Calorimetry; D011232:Chemical Precipitation; D006801:Humans; D006874:Hydrostatic Pressure; D010958:Plasminogen / Q000737:chemistry* / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D012756:Sheep; D013057:Spectrum Analysis; D013696:Temperature
D011328:Prions; D011480:Protease Inhibitors; D010958:Plasminogen