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The effect of β2‐α2 loop mutation on amyloidogenic properties of the prion protein
Author(s) -
Dutta Arpana,
Chen Shugui,
Surewicz Witold K.
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.07.023
Subject(s) - mutant , chemistry , prion protein , mutation , amyloid (mycology) , amino acid , protein folding , biophysics , wild type , biochemistry , biology , gene , disease , pathology , medicine , inorganic chemistry
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.