Species-dependent differences in cofactor utilization for formation of the protease-resistant prion protein in vitro.
The cofactor preferences for in vitro propagation of the protease-resistant isoforms of the prion protein (PrP(Sc)) from various rodent species were investigated using the serial protein misfolding cyclic amplification (sPMCA) technique. Whereas RNA molecules facilitate hamster PrP(Sc) propagation, RNA and several other polyanions do not promote the propagation of mouse and vole PrP(Sc) molecules. Pretreatment of crude Prnp(0/0) (PrP knockout) brain homogenate with RNase A or micrococcal nuclease inhibited hamster but not mouse PrP(Sc) propagation in a reconstituted system. Mouse PrP(Sc) propagation could be reconstituted by mixing PrP(C) substrate with homogenates prepared from either brain or liver, but not from several other tissues that were tested. These results reveal species-specific differences in cofactor utilization for PrP(Sc) propagation in vitro and also demonstrate the existence of an endogenous cofactor present in brain tissue not composed of nucleic acids.
Deleault
Nathan R
NR
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Kascsak
Richard
R
Geoghegan
James C
JC
Supattapone
Surachai
S
D000818:Animals; D003411:Arvicolinae; D016466:CHO Cells; D003067:Coenzymes / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D051379:Mice; D010447:Peptide Hydrolases / Q000737:chemistry*; D018620:PrPSc Proteins / Q000737:chemistry*; D011485:Protein Binding; D055550:Protein Stability; D012313:RNA / Q000737:chemistry; D051381:Rats; D013045:Species Specificity
D003067:Coenzymes; D018620:PrPSc Proteins; D012313:RNA; D010447:Peptide Hydrolases