A molecular switch controls interspeciesprion disease transmission in mice
2010 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 120, 2590-2599 p.Article in journal (Refereed) Published
Transmissible spongiform encephalopathies are lethal neurodegenerative disorders that present with aggregated forms of the cellular prion protein (PrPC), which are known as PrPSc. Prions from different species vary considerably in their transmissibility to xenogeneic hosts. The variable transmission barriers depend on sequence differences between incoming PrPSc and host PrPC and additionally, on strain-dependent conformational properties of PrPSc. The β2-α2 loop region within PrPC varies substantially between species, with its structure being influenced by the residue types in the 2 amino acid sequence positions 170 (most commonly S or N) and 174 (N or T). In this study, we inoculated prions from 5 different species into transgenic mice expressing either disordered-loop or rigid-loop PrPC variants. Similar β2-α2 loop structures correlated with efficient transmission, whereas dissimilar loops correlated with strong transmission barriers. We then classified literature data on cross-species transmission according to the 170S/N polymorphism. Transmission barriers were generally low between species with the same amino acid residue in position 170 and high between those with different residues. These findings point to a triggering role of the local β2-α2 loop structure for prion transmissibility between different species.
Place, publisher, year, edition, pages
American Society for Clinical Investigation , 2010. Vol. 120, 2590-2599 p.
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-73483DOI: 10.1172/JCI42051OAI: oai:DiVA.org:liu-73483DiVA: diva2:473028