論文

査読有り
2017年12月

Structural analysis of the STAT1:STAT2 heterodimer revealed the mechanism of Sendai virus C protein-mediated blockade of type 1 interferon signaling

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Kosuke Oda
  • ,
  • Takashi Oda
  • ,
  • Yasuyuki Matoba
  • ,
  • Mamoru Sato
  • ,
  • Takashi Irie
  • ,
  • Takemasa Sakaguchi

292
48
開始ページ
19752
終了ページ
19766
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M117.786285
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Sendai virus (SeV), which causes respiratory diseases in rodents, possesses the C protein that blocks the signal transduction of interferon (IFN), thereby escaping from host innate immunity. We previously demonstrated by using protein crystallography that two molecules of Y3 (the C-terminal half of the C protein) can bind to the homodimer of the N-terminal domain of STAT1 (STAT1ND), elucidating the mechanism of inhibition of IFN- signal transduction. SeV C protein also blocks the signal transduction of IFN-/ by inhibiting the phosphorylation of STAT1 and STAT2, although the mechanism for the inhibition is unclear. Therefore, we sought to elucidate the mechanism of inhibition of the IFN signal transduction via STAT1 and STAT2. Small angle X-ray scattering analysis indicated that STAT1ND associates with the N-terminal domain of STAT2 (STAT2ND) with the help of a Gly-rich linker. We generated a linker-less recombinant protein possessing a STAT1ND:STAT2ND heterodimeric structure via an artificial disulfide bond. Analytical size-exclusion chromatography and surface plasmon resonance revealed that one molecule of Y3 can associate with a linker-less recombinant protein. We propose that one molecule of C protein associates with the STAT1:STAT2 heterodimer, inducing a conformational change to an antiparallel form, which is easily dephosphorylated. This suggests that association of C protein with the STAT1ND:STAT2ND heterodimer is an important factor to block the IFN-/ signal transduction.

Web of Science ® 被引用回数 : 3

リンク情報
DOI
https://doi.org/10.1074/jbc.M117.786285
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28978648
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000416911300020&DestApp=WOS_CPL

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