RRC ID 52409
Author Oda K, Oda T, Matoba Y, Sato M, Irie T, Sakaguchi T.
Title Structural analysis of the STAT1:STAT2 heterodimer revealed the mechanism of Sendai virus C protein-mediated blockade of type 1 interferon signaling.
Journal J Biol Chem
Abstract 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-γ signal transduction. SeV C protein also blocks the signal transduction of IFN-α/β 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-α/β signal transduction.
Volume 292(48)
Pages 19752-19766
Published 2017-12-1
DOI 10.1074/jbc.M117.786285
PII M117.786285
PMID 28978648
PMC PMC5712616
MeSH Cell Line Crystallography, X-Ray Dimerization Humans Interferon Type I / metabolism* Phosphorylation Protein Conformation STAT1 Transcription Factor / chemistry STAT1 Transcription Factor / metabolism* STAT2 Transcription Factor / chemistry STAT2 Transcription Factor / metabolism* Sendai virus / metabolism* Signal Transduction* Viral Proteins / metabolism*
IF 4.106
Times Cited 3
Resource
Human and Animal Cells 293T(RCB2202)