Conversion efficiency of bank vole prion protein in vitro is determined by residues 155 and 170, but does not correlate with the high susceptibility of bank voles to sheep scrapie in vivo.
The misfolded infectious isoform of the prion protein (PrP(Sc)) is thought to replicate in an autocatalytic manner by converting the cellular form (PrP(C)) into its pathogenic folding variant. The similarity in the amino acid sequence of PrP(C) and PrP(Sc) influences the conversion efficiency and is considered as the major determinant for the species barrier. We performed in vitro conversion reactions on wild-type and mutated PrP(C) to determine the role of the primary sequence for the high susceptibility of bank voles to scrapie. Different conversion efficiencies obtained with bank vole and mouse PrP(C) in reactions with several prion strains were due to differences at amino acid residues 155 and 170. However, the conversion efficiencies obtained with mouse and vole PrP(C) in reactions with sheep scrapie did not correlate with the susceptibility of the respective species to this prion strain. This discrepancy between in vitro and in vivo data may indicate that at least in the case of scrapie transmission to bank voles additional host factors can strongly modulate the species barrier. Furthermore, in vitro conversion reactions with different prion strains revealed that the degree of alteration of the conversion efficiency induced by amino acid exchanges was varying according to the prion strain. These results support the assumption that the repertoire of conformations adopted by a certain PrP(C) primary sequence is decisive for its convertibility to the strain-specific PrP(Sc) conformation.
Piening
Niklas
N
Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität, Feodor-Lynen-Strasse 23, 81377 Munich, Germany.
Nonno
Romolo
R
Di Bari
Michele
M
Walter
Stephanie
S
Windl
Otto
O
Agrimi
Umberto
U
Kretzschmar
Hans A
HA
Bertsch
Uwe
U
D000595:Amino Acid Sequence; D000818:Animals; D003411:Arvicolinae / Q000502:physiology*; D004198:Disease Susceptibility; D051379:Mice; D008969:Molecular Sequence Data; D018621:PrPC Proteins / Q000737:chemistry*; D018620:PrPSc Proteins / Q000737:chemistry*; D011487:Protein Conformation; D012608:Scrapie / Q000635:transmission*; D012756:Sheep
D018621:PrPC Proteins; D018620:PrPSc Proteins