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

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 var...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sudheer Babu Sangeetham, Anna Dorothee Engelke, Elfrieda Fodor, Sarah Laura Krausz, Jörg Tatzelt, Ervin Welker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c043bbcf337e4e7aaaff2a79aaf27566
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c043bbcf337e4e7aaaff2a79aaf27566
record_format	dspace
spelling	oai:doaj.org-article:c043bbcf337e4e7aaaff2a79aaf275662021-12-02T10:44:15ZThe G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo10.1038/s41598-021-82647-w2045-2322https://doaj.org/article/c043bbcf337e4e7aaaff2a79aaf275662021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82647-whttps://doaj.org/toc/2045-2322Abstract 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.Sudheer Babu SangeethamAnna Dorothee EngelkeElfrieda FodorSarah Laura KrauszJörg TatzeltErvin WelkerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sudheer Babu Sangeetham Anna Dorothee Engelke Elfrieda Fodor Sarah Laura Krausz Jörg Tatzelt Ervin Welker The G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo
description	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.
format	article
author	Sudheer Babu Sangeetham Anna Dorothee Engelke Elfrieda Fodor Sarah Laura Krausz Jörg Tatzelt Ervin Welker
author_facet	Sudheer Babu Sangeetham Anna Dorothee Engelke Elfrieda Fodor Sarah Laura Krausz Jörg Tatzelt Ervin Welker
author_sort	Sudheer Babu Sangeetham
title	The G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo
title_short	The G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo
title_full	The G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo
title_fullStr	The G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo
title_full_unstemmed	The G127V variant of the prion protein interferes with dimer formation in vitro but not in cellulo
title_sort	g127v variant of the prion protein interferes with dimer formation in vitro but not in cellulo
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c043bbcf337e4e7aaaff2a79aaf27566
work_keys_str_mv	AT sudheerbabusangeetham theg127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT annadorotheeengelke theg127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT elfriedafodor theg127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT sarahlaurakrausz theg127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT jorgtatzelt theg127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT ervinwelker theg127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT sudheerbabusangeetham g127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT annadorotheeengelke g127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT elfriedafodor g127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT sarahlaurakrausz g127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT jorgtatzelt g127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo AT ervinwelker g127vvariantoftheprionproteininterfereswithdimerformationinvitrobutnotincellulo
_version_	1718396787379666944

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

Ejemplares similares