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A short peptide at the amino terminus of the Sendai virus C protein acts as an independent element that induces STAT1 instability |
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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 Sequence — Cell Line — DNA-Binding Proteins/metabolism — Gene Expression Regulation — Green Fluorescent Proteins — Humans — Luminescent Proteins/genetics/metabolism — Molecular Sequence Data — Mutagenesis — Peptides/chemistry/genetics/metabolism — Protein Folding — Recombinant Fusion Proteins/genetics/metabolism — STAT1 Transcription Factor — Sendai virus/pathogenicity — Signal Transduction — Structure-Activity Relationship — Trans-Activators/metabolism — Viral Proteins/chemistry/genetics/metabolism | |
Identifiers | PMID: 15280488 | |
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Research group | Virologie moléculaire (275) | |
Citation (ISO format) | 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. doi: 10.1128/JVI.78.16.8799-8811.2004 https://archive-ouverte.unige.ch/unige:38143 |