The Molecular Basis for E<sup>rns</sup> Dimerization in Classical Swine Fever Virus

The pestivirus classical swine fever virus (CSFV) represents one of the most important pathogens of swine. Its virulence is dependent on the RNase activity of the essential structural glycoprotein E<sup>rns</sup> that uses an amphipathic helix as a membrane anchor and forms homodimers vi...

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Autores principales:	Manjula Mischler, Gregor Meyers
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pestivirus flavivirus envelope protein dimerization of glycoprotein amphipathic helix disulfide bond formation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1c8256f650444128b56cb0eebbd89c50
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spelling	oai:doaj.org-article:1c8256f650444128b56cb0eebbd89c502021-11-25T19:13:18ZThe Molecular Basis for E<sup>rns</sup> Dimerization in Classical Swine Fever Virus10.3390/v131122041999-4915https://doaj.org/article/1c8256f650444128b56cb0eebbd89c502021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2204https://doaj.org/toc/1999-4915The pestivirus classical swine fever virus (CSFV) represents one of the most important pathogens of swine. Its virulence is dependent on the RNase activity of the essential structural glycoprotein E<sup>rns</sup> that uses an amphipathic helix as a membrane anchor and forms homodimers via disulfide bonds employing cysteine 171. Dimerization is not necessary for CSFV viability but for its virulence. Mutant E<sup>rns</sup> proteins lacking cysteine 171 are still able to interact transiently as shown in crosslink experiments. Deletion analysis did not reveal the presence of a primary sequence-defined contact surface essential for dimerization, but indicated a general importance of an intact ectodomain for efficient establishment of dimers. Pseudoreverted viruses reisolated in earlier experiments from pigs with mutations Cys171Ser/Ser209Cys exhibited partially restored virulence and restoration of the ability to form E<sup>rns</sup> homodimers. Dimer formation was also observed for experimentally mutated proteins, in which other amino acids at different positions of the membrane anchor region of E<sup>rns</sup> were replaced by cysteine. However, with one exception of two very closely located residues, the formation of disulfide-linked dimers was only observed for cysteine residues located at the same position of the helix.Manjula MischlerGregor MeyersMDPI AGarticlepestivirusflavivirusenvelope proteindimerization of glycoproteinamphipathic helixdisulfide bond formationMicrobiologyQR1-502ENViruses, Vol 13, Iss 2204, p 2204 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pestivirus flavivirus envelope protein dimerization of glycoprotein amphipathic helix disulfide bond formation Microbiology QR1-502
spellingShingle	pestivirus flavivirus envelope protein dimerization of glycoprotein amphipathic helix disulfide bond formation Microbiology QR1-502 Manjula Mischler Gregor Meyers The Molecular Basis for E<sup>rns</sup> Dimerization in Classical Swine Fever Virus
description	The pestivirus classical swine fever virus (CSFV) represents one of the most important pathogens of swine. Its virulence is dependent on the RNase activity of the essential structural glycoprotein E<sup>rns</sup> that uses an amphipathic helix as a membrane anchor and forms homodimers via disulfide bonds employing cysteine 171. Dimerization is not necessary for CSFV viability but for its virulence. Mutant E<sup>rns</sup> proteins lacking cysteine 171 are still able to interact transiently as shown in crosslink experiments. Deletion analysis did not reveal the presence of a primary sequence-defined contact surface essential for dimerization, but indicated a general importance of an intact ectodomain for efficient establishment of dimers. Pseudoreverted viruses reisolated in earlier experiments from pigs with mutations Cys171Ser/Ser209Cys exhibited partially restored virulence and restoration of the ability to form E<sup>rns</sup> homodimers. Dimer formation was also observed for experimentally mutated proteins, in which other amino acids at different positions of the membrane anchor region of E<sup>rns</sup> were replaced by cysteine. However, with one exception of two very closely located residues, the formation of disulfide-linked dimers was only observed for cysteine residues located at the same position of the helix.
format	article
author	Manjula Mischler Gregor Meyers
author_facet	Manjula Mischler Gregor Meyers
author_sort	Manjula Mischler
title	The Molecular Basis for E<sup>rns</sup> Dimerization in Classical Swine Fever Virus
title_short	The Molecular Basis for E<sup>rns</sup> Dimerization in Classical Swine Fever Virus
title_full	The Molecular Basis for E<sup>rns</sup> Dimerization in Classical Swine Fever Virus
title_fullStr	The Molecular Basis for E<sup>rns</sup> Dimerization in Classical Swine Fever Virus
title_full_unstemmed	The Molecular Basis for E<sup>rns</sup> Dimerization in Classical Swine Fever Virus
title_sort	molecular basis for e<sup>rns</sup> dimerization in classical swine fever virus
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1c8256f650444128b56cb0eebbd89c50
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The Molecular Basis for E<sup>rns</sup> Dimerization in Classical Swine Fever Virus

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