Identification of a Homology-Independent Linchpin Domain Controlling Mouse and Bank Vole Prion Protein Conversion

Cassandra M. Burke, Kenneth M. K. Mark, Daniel J. Walsh , Geoffrey P. Noble , Alexander D. Steele, Abigail Diack, Jean Manson, Joel C. Watts, Surachai Supattapone

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Abstract: Prions are unorthodox pathogens that cause fatal neurodegenerative diseases in humans and other mammals. Prion propagation occurs through the self-templating of the pathogenic conformer PrPSc, onto the cell-expressed conformer, PrPC. Here we study the conversion of PrPC to PrPSc using a recombinant mouse PrPSc conformer (mouse protein-only recPrPSc) as a unique tool that can convert bank vole but not mouse PrPC substrates in vitro. Thus, its templating ability is not dependent on sequence homology with the substrate. In the present study, we used chimeric bank vole/mouse PrPC substrates to systematically determine the domain that allows for conversion by Mo protein-only recPrPSc. Our results show that that either the presence of the bank vole amino acid residues E227 and S230 or the absence of the second N-linked glycan are sufficient to allow PrPC substrates to be converted by Mo protein-only recPrPSc and several native infectious prion strains. We propose that residues 227 and 230 and the second glycan are part of a C-terminal domain that acts as a linchpin for bank vole and mouse prion conversion.
Original languageEnglish
JournalPLoS Pathogens
Early online date8 Sept 2020
Publication statusE-pub ahead of print - 8 Sept 2020


Dive into the research topics of 'Identification of a Homology-Independent Linchpin Domain Controlling Mouse and Bank Vole Prion Protein Conversion'. Together they form a unique fingerprint.

Cite this