A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers

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A key prediction of the prion hypothesis is that autocatalytic, misfolded PrPSc molecules should be highly infectious. Various recombinant PrPSc conformers are able to self-propagate in vitro, yet paradoxically only some of these conformers possess significant levels of specific infectivity in bioassays. Here we use two closely-matched autocatalytic recombinant PrP conformers that share the same origin but differ by >105-fold in specific infectivity to study the molecular basis of prion infectivity. We show that infectious and non-infectious autocatalytic recombinant PrP conformers have subtle structural differences, and that GPI-anchored PrP substrate molecules can only adopt the infectious PrPSc conformation. We conclude that post-translational modifications of host PrPC molecules play a critical role in restricting the range of recombinant PrPSc conformers that are biologically infectious.

Vyšlo v časopise: A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1005017
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005017

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