The G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo

Sci Rep. 2021 Feb 4;11(1):3116. doi: 10.1038/s41598-021-82647-w.

Abstract

Scrapie prion, PrPSc, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Cloning, Molecular
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Glycine / chemistry
  • Glycine / metabolism*
  • HeLa Cells
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Molecular Dynamics Simulation
  • Mutation
  • PrPSc Proteins / chemistry*
  • PrPSc Proteins / genetics
  • PrPSc Proteins / metabolism
  • Prion Diseases / genetics
  • Prion Diseases / metabolism
  • Prion Proteins / chemistry*
  • Prion Proteins / genetics
  • Prion Proteins / metabolism
  • Protein Multimerization
  • Recombinant Fusion Proteins / chemistry*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Valine / chemistry
  • Valine / metabolism*

Substances

  • Luminescent Proteins
  • PrPSc Proteins
  • Prion Proteins
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • red fluorescent protein
  • Valine
  • Glycine