First Author | Anaya ZE | Year | 2011 |
Journal | J Biol Chem | Volume | 286 |
Issue | 10 | Pages | 8141-8 |
PubMed ID | 21212268 | Mgi Jnum | J:170530 |
Mgi Id | MGI:4946844 | Doi | 10.1074/jbc.M110.165233 |
Citation | Anaya ZE, et al. (2011) Recovery of small infectious PrP(res) aggregates from prion-infected cultured cells. J Biol Chem 286(10):8141-8 |
abstractText | Prion diseases are characterized by deposits of abnormal conformers of the PrP protein. Although large aggregates of proteinase K-resistant PrP (PrP(res)) are infectious, the precise relationships between aggregation state and infectivity remain to be established. In this study, we have fractionated detergent lysates from prion-infected cultured cells by differential ultracentrifugation and ultrafiltration and have characterized a previously unnoticed PrP species. This abnormal form is resistant to proteinase K digestion but, in contrast to typical aggregated PrP(res), remains in the soluble fraction at intermediate centrifugal forces and is not retained by filters of 300-kDa cutoff. Cell-based assay and inoculation to animals demonstrate that these entities are infectious. The finding that cell-derived small infectious PrP(res) aggregates can be recovered in the absence of strong in vitro denaturating treatments now gives a biological basis for investigating the role of small PrP aggregates in the pathogenicity and/or the multiplication cycle of prions. |