The effect of β2-α2 loop mutation on amyloidogenic properties of the prion protein

•Rigid loop variant of mouse prion protein shows increased amyloidogenicity.•Amyloid fibrils of wild-type and rigid loop PrP variant are structurally similar.•The present data in vitro help explain previous observations in transgenic mice. Recent studies revealed that elk-like S170N/N174T mutation in mouse prion protein (moPrP), which results in an increased rigidity of β2-α2 loop, leads to a prion disease in transgenic mice. Here we characterized the effect of this mutation on biophysical properties of moPrP. Despite similar thermodynamic stabilities of wild type and mutant proteins, the latter was found to have markedly higher propensity to form amyloid fibrils. Importantly, this effect was observed even under fully denaturing conditions, indicating that the increased conversion propensity of the mutant protein is not due to loop rigidity but rather results from greater amyloidogenic potential of the amino acid sequence within the loop region of S170N/N174T moPrP. PrP and PrPbind by atomic force microscopy (View interaction) PrP and PrPbind by fluorescence technology (View interaction)