The Effect of Plasminogen-Derived Peptides to PrPSc Formation

Abstract

The disease-associated scrapie prion protein (PrPSc), the sole biochemical entity of prions, is formed from the cellular prion protein (PrP(c)) by conformational conversion. Previously, plasminogen was shown to interact with multiple PrP species. Hence, plasminogen was utilized not only to enrich the disease-associated PrP isoforms but also to stimulate the formation of PrPSc. Here, we report that incubation of prion-infected cultured cells with the peptides composed of unique YRG/YKRG motifs derived from plasminogen increased a marginal level of PrPSc. This phenomenon is attributed to enrichment of PrPSc by the plasminogen-derived peptide because incubation of the YRG peptide with cell lysate containing PrPSc resulted in an increase of their association, although this interaction was feasible only under a limited condition. The peptides did not increase PrPSc production in protein misfolding cyclic amplification assay, an in vitro reaction of PrP(c) conversion to PrPSc. Taken together, the results of this study suggest that the stimulatory activity of plasminogen in PrPSc formation is not conserved in the plasminogen-derived YRG/YKRG peptides that can physically associate with PrPSc.