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Title

A short peptide at the amino terminus of the Sendai virus C protein acts as an independent element that induces STAT1 instability

Authors
Martin, Stephen
Published in Journal of Virology. 2004, vol. 78, no. 16, p. 8799-811
Abstract The Sendai virus C protein acts to dismantle the interferon-induced cellular antiviral state in an MG132-sensitive manner, in part by inducing STAT1 instability. This activity of C maps to the first 23 amino acids (C(1-23)) of the 204-amino-acid (aa)-long protein (C(1-204)). C(1-23) was found to act as an independent viral element that induces STAT1 instability, since this peptide fused to green fluorescent protein (C(1-23)/GFP) is at least as active as C(1-204) in this respect. This peptide also induces the degradation of C(1-23)/GFP and other proteins to which it is fused. Most of C(1-204), and particularly its amino-terminal half, is predicted to be structurally disordered. C(1-23) as a peptide was found to be disordered by circular dichroism, and the first 11 aa have a strong potential to form an amphipathic alpha-helix in low concentrations of trifluoroethanol, which is thought to mimic protein-protein interaction. The critical degradation-determining sequence of C(1-23) was mapped by mutation to eight residues near its N terminus: (4)FLKKILKL(11). All the large hydrophobic residues of (4)FLKKILKL(11), plus its ability to form an amphipathic alpha-helix, were found to be critical for STAT1 degradation. In contrast, C(1-23)/GFP self-degradation did not require (8)ILKL(11), nor the ability to form an alpha-helix throughout this region. Remarkably, C(1-23)/GFP also stimulated C(1-204) degradation, and this degradation in trans required the same peptide determinants as for STAT1. Our results suggest that C(1-204) coordinates its dual activities of regulating viral RNA synthesis and counteracting the host innate antiviral response by sensing both its own intracellular concentration and that of STAT1.
Keywords Amino Acid SequenceCell LineDNA-Binding Proteins/metabolismGene Expression RegulationGreen Fluorescent ProteinsHumansLuminescent Proteins/genetics/metabolismMolecular Sequence DataMutagenesisPeptides/chemistry/genetics/metabolismProtein FoldingRecombinant Fusion Proteins/genetics/metabolismSTAT1 Transcription FactorSendai virus/pathogenicitySignal TransductionStructure-Activity RelationshipTrans-Activators/metabolismViral Proteins/chemistry/genetics/metabolism
Identifiers
PMID: 15280488
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Article (Published version) (1.9 MB) - public document Free access
Structures
Research group Virologie moléculaire (275)
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GARCIN, Dominique et al. A short peptide at the amino terminus of the Sendai virus C protein acts as an independent element that induces STAT1 instability. In: Journal of Virology, 2004, vol. 78, n° 16, p. 8799-811. https://archive-ouverte.unige.ch/unige:38143

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Deposited on : 2014-06-25

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