1. The G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo.
- Author
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Sangeetham SB, Engelke AD, Fodor E, Krausz SL, Tatzelt J, and Welker E
- Subjects
- Amino Acid Substitution, Cloning, Molecular, Escherichia coli genetics, Escherichia coli metabolism, Gene Expression, Genetic Vectors chemistry, Genetic Vectors metabolism, Glycine chemistry, HeLa Cells, Humans, Luminescent Proteins genetics, Luminescent Proteins metabolism, Molecular Dynamics Simulation, Mutation, PrPSc Proteins genetics, PrPSc Proteins metabolism, Prion Diseases genetics, Prion Diseases metabolism, Prion Proteins genetics, Prion Proteins metabolism, Protein Multimerization, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins metabolism, Valine chemistry, Red Fluorescent Protein, Glycine metabolism, PrPSc Proteins chemistry, Prion Proteins chemistry, Recombinant Fusion Proteins chemistry, Valine metabolism
- Abstract
Scrapie prion, PrP
Sc , formation is the central event of all types of transmissible spongiform encephalopathies (TSEs), while the pathway with possible intermediates and their mechanism of formation from the normal isoform of prion (PrP), remains not fully understood. Recently, the G127V variant of the human PrP is reported to render the protein refractory to transmission of TSEs, via a yet unknown mechanism. Molecular dynamics studies suggested that this mutation interferes with the formation of PrP dimers. Here we analyze the dimerization of 127G and 127VPrP, in both in vitro and a mammalian cell culture system. Our results show that while molecular dynamics may capture the features affecting dimerization in vitro, G127V inhibiting dimer formation of PrP, these are not evidenced in a more complex cellular system.- Published
- 2021
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