Structural basis of the inhibition of STAT1 activity by Sendai virus C protein

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860341
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Virology
• Research Institution: Hiroshima University
• Principal Investigator: ODA Kosuke 広島大学, 大学院医歯薬保健学研究院, 助教 (60571255)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 構造生物 / 自然免疫 / パラミクソウイルス / インターフェロン / FRET

Outline of Final Research Achievements

Sendai virus C protein inhibits the signal transduction pathways of interferon-γ by binding to the N-terminal domain of STAT1 (STAT1ND). We determined the crystal structure of STAT1ND associated with the C-terminal half of the C protein (Y3). The structure showed that two molecules of Y3 symmetrically bind to each niche created between two molecules of the STAT1ND dimer. Molecular modeling suggested that an anti-parallel form of the full-length STAT1 dimer can bind only one Y3 molecule and that a parallel form can bind two Y3 molecules.　Our study suggests that C protein interferes with the domain arrangement of STAT1 dimer, leading to the accumulation of phosphorylated STAT1 and the formation of high molecular weight complex in slower kinetic, which is responsible to complete inhibition of transcription. In addition, we discuss the underlying mechanism that the phosphorylation of STAT2 is inhibited in the presence of the C protein after stimulation by IFN-α/β.

Free Research Field

ウイルス学