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The role of glycophosphatidylinositol anchor in the amplification of the scrapie isoform of prion protein in vitro
Author(s) -
Kim Jae-Il,
Surewicz Krystyna,
Gambetti Pierluigi,
Surewicz Witold K.
Publication year - 2009
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.2009.10.049
Subject(s) - gene isoform , scrapie , recombinant dna , prion protein , autocatalysis , in vitro , transmissible spongiform encephalopathy , chemistry , protein folding , protease , biochemistry , biology , microbiology and biotechnology , enzyme , gene , medicine , disease , pathology , catalysis
Transmissible spongiform encephalopathies are associated with an autocatalytic conversion of normal prion protein, PrP C , to a protease‐resistant form, PrPres. This autocatalytic reaction can be reproduced in vitro using a procedure called protein misfolding cyclic amplification (PMCA). Here we show that, unlike brain‐derived PrP C , bacterially‐expressed recombinant prion protein (rPrP) is a poor substrate for PrPres amplification in a standard PMCA reaction. The differences between PrP C and rPrP appear to be due to the lack of the glycophosphatidylinositol anchor in the recombinant protein. These findings shed a new light on prion protein conversion process and have important implications for the efforts to generate synthetic prions for structural and biophysical studies.