Author:
Sangeetham Sudheer Babu,Engelke Anna Dorothee,Fodor Elfrieda,Krausz Sarah Laura,Tatzelt Jörg,Welker Ervin
Abstract
AbstractScrapie 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.
Funder
The National Research, Development and Innovation Office
Deutsche Forschungsgemeinschaft
Germany's Excellence Strategy
The Ministry of National Economy
Publisher
Springer Science and Business Media LLC
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