The region approximately between amino acids 81 and 137 of proteinase K-resistant PrPSc is critical for the infectivity of the Chandler prion strain.
Although the major component of the prion is believed to be the oligomer of PrP(Sc), little information is available concerning regions on the PrP(Sc) molecule that affect prion infectivity. During the analysis of PrP(Sc) molecules from various prion strains, we found that PrP(Sc) of the Chandler strain showed a unique property in the conformational-stability assay, and this property appeared to be useful for studying the relationship between regions of the PrP(Sc) molecule and prion infectivity. Thus, we analyzed PrP(Sc) of the Chandler strain in detail and analyzed the infectivities of the N-terminally denatured and truncated forms of proteinase K-resistant PrP. The N-terminal region of PrP(Sc) of the Chandler strain showed region-dependent resistance to guanidine hydrochloride (GdnHCl) treatment. The region approximately between amino acids (aa) 81 and 137 began to be denatured by treatment with 1.5 M GdnHCl. Within this stretch, the region comprising approximately aa 81 to 90 was denatured almost completely by 2 M GdnHCl. Furthermore, the region approximately between aa 90 and 137 was denatured completely by 3 M GdnHCl. However, the C-terminal region thereafter was extremely resistant to the GdnHCl treatment. This property was not observed in PrP(Sc) molecules of other prion strains. Denaturation of the region between aa 81 and 137 by 3 M GdnHCl significantly prolonged the incubation periods in mice compared to that for the untreated control. More strikingly, the denaturation and removal of this region nearly abolished the infectivity. This finding suggests that the conformation of the region between aa 81 and 137 of the Chandler strain PrP(Sc) molecule is directly associated with prion infectivity.
Shindoh
Ryo
R
Laboratory of Prion Diseases, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
Kim
Chan-Lan
CL
Song
Chang-Hyun
CH
Hasebe
Rie
R
Horiuchi
Motohiro
M
D000596:Amino Acids / Q000235:genetics / Q000502:physiology*; D000818:Animals; D019286:Endopeptidase K / Q000378:metabolism; D019791:Guanidine / Q000378:metabolism; D051379:Mice; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D017096:Prion Diseases / Q000517:prevention & control; D011487:Protein Conformation; D011489:Protein Denaturation; D017384:Sequence Deletion; D013997:Time Factors
D000596:Amino Acids; D018620:PrPSc Proteins; D019286:Endopeptidase K; D019791:Guanidine