The Presence of the Iron-Sulfur Motif Is Important for the Conformational Stability of the Antiviral Protein, Viperin
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
The Presence of the Iron-Sulfur Motif Is Important for the
Conformational Stability of the Antiviral Protein, Viperin
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| Creator |
Haldar, Shubhasis
Paul, Simantasarani Joshi, Nidhi Dasgupta, Anindya Chattopadhyay, Krishnananda |
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| Subject |
Infectious Diseases and Immunology
Structural Biology & Bioinformatics |
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| Description |
Viperin, an antiviral protein, has been shown to contain a CX3CX2C motif, which is conserved in the radical S-adenosylmethionine
(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 a -b 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.
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| Date |
2012
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1540/1/PLOS_ONE__7(_2_)_Article_Number_e31797;2012[50].pdf
Haldar, Shubhasis and Paul, Simantasarani and Joshi, Nidhi and Dasgupta, Anindya and Chattopadhyay, Krishnananda (2012) The Presence of the Iron-Sulfur Motif Is Important for the Conformational Stability of the Antiviral Protein, Viperin. LPLoS ONE, 7 (2). e31797. |
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| Relation |
http://dx.doi.org/10.1371/journal.pone.0031797
http://www.eprints.iicb.res.in/1540/ |
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