The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.

Viperin, an antiviral protein, has been shown to contain a CX(3)CX(2)C motif, which is conserved in the radical S-adenosyl-methionine (SAM) enzyme family. A triple mutant which replaces these three cysteines with alanines has been shown to have severe deficiency in antiviral activity. Since the crys...

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Autores principales:	Shubhasis Haldar, Simantasarani Paul, Nidhi Joshi, Anindya Dasgupta, Krishnananda Chattopadhyay
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2fc1e933accd4621b36c3839bd4a3813
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spelling	oai:doaj.org-article:2fc1e933accd4621b36c3839bd4a38132021-12-02T20:15:57ZThe presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.1932-620310.1371/journal.pone.0031797https://doaj.org/article/2fc1e933accd4621b36c3839bd4a38132012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22363738/?tool=EBIhttps://doaj.org/toc/1932-6203Viperin, an antiviral protein, has been shown to contain a CX(3)CX(2)C motif, which is conserved in the radical S-adenosyl-methionine (SAM) enzyme family. A triple mutant which replaces these three cysteines with alanines has been shown to have severe deficiency in antiviral activity. Since the crystal structure of Viperin is not available, we have used a combination of computational methods including multi-template homology modeling and molecular dynamics simulation to develop a low-resolution predicted structure. The results show that Viperin is an α-β protein containing iron-sulfur cluster at the center pocket. The calculations suggest that the removal of iron-sulfur cluster would lead to collapse of the protein tertiary structure. To verify these predictions, we have prepared, expressed and purified four mutant proteins. In three mutants individual cysteine residues were replaced by alanine residues while in the fourth all the cysteines were replaced by alanines. Conformational analyses using circular dichroism and steady state fluorescence spectroscopy indicate that the mutant proteins are partially unfolded, conformationally unstable and aggregation prone. The lack of conformational stability of the mutant proteins may have direct relevance to the absence of their antiviral activity.Shubhasis HaldarSimantasarani PaulNidhi JoshiAnindya DasguptaKrishnananda ChattopadhyayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e31797 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shubhasis Haldar Simantasarani Paul Nidhi Joshi Anindya Dasgupta Krishnananda Chattopadhyay The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.
description	Viperin, an antiviral protein, has been shown to contain a CX(3)CX(2)C motif, which is conserved in the radical S-adenosyl-methionine (SAM) enzyme family. A triple mutant which replaces these three cysteines with alanines has been shown to have severe deficiency in antiviral activity. Since the crystal structure of Viperin is not available, we have used a combination of computational methods including multi-template homology modeling and molecular dynamics simulation to develop a low-resolution predicted structure. The results show that Viperin is an α-β protein containing iron-sulfur cluster at the center pocket. The calculations suggest that the removal of iron-sulfur cluster would lead to collapse of the protein tertiary structure. To verify these predictions, we have prepared, expressed and purified four mutant proteins. In three mutants individual cysteine residues were replaced by alanine residues while in the fourth all the cysteines were replaced by alanines. Conformational analyses using circular dichroism and steady state fluorescence spectroscopy indicate that the mutant proteins are partially unfolded, conformationally unstable and aggregation prone. The lack of conformational stability of the mutant proteins may have direct relevance to the absence of their antiviral activity.
format	article
author	Shubhasis Haldar Simantasarani Paul Nidhi Joshi Anindya Dasgupta Krishnananda Chattopadhyay
author_facet	Shubhasis Haldar Simantasarani Paul Nidhi Joshi Anindya Dasgupta Krishnananda Chattopadhyay
author_sort	Shubhasis Haldar
title	The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.
title_short	The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.
title_full	The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.
title_fullStr	The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.
title_full_unstemmed	The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.
title_sort	presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, viperin.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/2fc1e933accd4621b36c3839bd4a3813
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The presence of the iron-sulfur motif is important for the conformational stability of the antiviral protein, Viperin.

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