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

Sangeetham, Sudheer Babu and Engelke, A.D. and Ayaydin-Fodor, Elfrieda and Krausz, Sarah and Tatzelt, J. and Welker, Ervin (2021) The G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo. SCIENTIFIC REPORTS, 11 (1). ISSN 2045-2322

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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. © 2021, The Author(s).

Item Type: Article
Additional Information: Institute of Biochemistry, Biological Research Centre, Szeged, 6726, Hungary Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Dugonics square 13, Szeged, 6720, Hungary Department Biochemistry of Neurodegenerative Diseases, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum, 44801, Germany Institute of Enzymology, Research Centre for Natural Sciences, Budapest, 1117, Hungary School of Ph.D. Studies, Semmelweis University, Budapest, 1085, Hungary Aktogen Hungary Ltd., Kecskemét, 6000, Hungary Cluster of Excellence RESOLV, Bochum, Germany Department of Neurology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, 40225, Germany Export Date: 30 May 2021 Correspondence Address: Welker, E.; Institute of Biochemistry, Hungary; email: welker.ervin@brc.hu Correspondence Address: Tatzelt, J.; Department Biochemistry of Neurodegenerative Diseases, Germany; email: Joerg.Tatzelt@ruhr-uni-bochum.de
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 07 Feb 2022 14:42
Last Modified: 07 Feb 2022 14:42
URI: http://real.mtak.hu/id/eprint/137536

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