| First Author | Choi JK | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 48 | Pages | 13851-13856 |
| PubMed ID | 27849581 | Mgi Jnum | J:239097 |
| Mgi Id | MGI:5824941 | Doi | 10.1073/pnas.1610716113 |
| Citation | Choi JK, et al. (2016) Amyloid fibrils from the N-terminal prion protein fragment are infectious. Proc Natl Acad Sci U S A 113(48):13851-13856 |
| abstractText | Recombinant C-terminally truncated prion protein PrP23-144 (which corresponds to the Y145Stop PrP variant associated with a Gerstmann-Straussler-Scheinker-like prion disease) spontaneously forms amyloid fibrils with a parallel in-register beta-sheet architecture and beta-sheet core mapping to residues approximately 112-139. Here we report that mice (both tga20 and wild type) inoculated with a murine (moPrP23-144) version of these fibrils develop clinical prion disease with a 100% attack rate. Remarkably, even though fibrils in the inoculum lack the entire C-terminal domain of PrP, brains of clinically sick mice accumulate longer proteinase K-resistant (PrPres) fragments of approximately 17-32 kDa, similar to those observed in classical scrapie strains. Shorter, Gerstmann-Straussler-Scheinker-like PrPres fragments are also present. The evidence that moPrP23-144 amyloid fibrils generated in the absence of any cofactors are bona fide prions provides a strong support for the protein-only hypothesis of prion diseases in its pure form, arguing against the notion that nonproteinaceous cofactors are obligatory structural components of all infectious prions. Furthermore, our finding that a relatively short beta-sheet core of PrP23-144 fibrils (residues approximately 112-139) with a parallel in-register organization of beta-strands is capable of seeding the conversion of full-length prion protein to the infectious form has important implications for the ongoing debate regarding structural aspects of prion protein conversion and molecular architecture of mammalian prions. |
