The C-terminal half-fragment of the Sendai virus C protein prevents the gamma-activated factor from binding to a gamma-activated sequence site.
Sendai virus C protein associates with the signal transducer and activator of transcription (STAT) 1 and inhibits the interferon (IFN) response. We report a molecular basis for the anti-IFN-gamma mechanism of Sendai virus. The C-terminal half-fragment of the C protein (D1) retains both the STAT1-binding and the anti-IFN-gamma abilities comparable to those of the full-size C. IFN-gamma stimulation generates phosphorylated-STAT1 even in the presence of the C or the D1. The phosphorylated-STAT1 generated in the D1-expressing cells forms an aberrant complex, which does not bind to a gamma-activated sequence (GAS) probe. Purified D1, indeed, inhibits in vitro the binding of the phosphorylated-STAT1 dimer to the GAS probe. The D1, however, binds to the STAT1 N-terminal domain, but not the DNA binding domain. These results suggest the possibility that the C protein prevents the gamma-activated factor from binding to GAS elements through its interaction with the STAT1 N-terminal domain.
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaizuki 23-3, Matsuoka-cho, Yoshida-gun, 910-1193, Fukui, Japan. bin@fmsrsa.fukui-med.ac.jp
Bin
B
Gotoh
Takayuki
T
Komatsu
Kenji
K
Takeuchi
Junko
J
Yokoo
D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D050794:STAT1 Transcription Factor; D029082:Sendai virus / Q000378:metabolism / Q000472:pathogenicity*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; D007371:Interferon-gamma