Structural Basis of the Inhibition of STAT1 Activity by Sendai Virus C Protein

Journal of Virology
Kosuke OdaTakemasa Sakaguchi

Abstract

Sendai virus (SeV) C protein inhibits the signal transduction pathways of interferon alpha/beta (IFN-α/β) and IFN-γ by binding to the N-terminal domain of STAT1 (STAT1ND), thereby allowing SeV to escape from host innate immunity. Here we determined the crystal structure of STAT1ND associated with the C-terminal half of the C protein (Y3 [amino acids 99 to 204]) at a resolution of 2.0 Å. This showed that two molecules of Y3 symmetrically bind to each niche created between two molecules of the STAT1ND dimer. Molecular modeling suggested that an antiparallel form of the full-length STAT1 dimer can bind only one Y3 molecule and that a parallel form can bind two Y3 molecules. Affinity analysis demonstrated anticooperative binding of two Y3 molecules with the STAT1 dimer, which is consistent with the hypothetical model that the second Y3 molecule can only target the STAT1 dimer in a parallel form. STAT1 with excess amounts of Y3 was prone to inhibit the dephosphorylation at Tyr(701) by a phosphatase. In an electrophoretic mobility shift assay, tyrosine-phosphorylated STAT1 (pY-STAT1) with Y3 associated with the γ-activated sequence, probably as high-molecular-weight complexes (HMWCs), which may account for partial inhibition of a rep...Continue Reading

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Citations

Aug 4, 2016·Journal of Molecular Biology·Srirupa ChatterjeeDaisy W Leung
May 5, 2017·Journal of Virology·Vidyanath ChaudharyDong-Yan Jin
Nov 22, 2019·Journal of Virology·Christian K PfallerRoberto Cattaneo
Jun 26, 2020·Journal of Virology·Yuma NaganoToyoyuki Ose
Jan 24, 2019·Frontiers in Immunology·Hao-Sen Chiang, Helene Minyi Liu
Nov 14, 2019·Cell Reports·Md Alamgir HossainPaul R Gooley
Nov 27, 2020·Journal of Virology·Oliver SieringChristian K Pfaller
Apr 10, 2021·Frontiers in Cell and Developmental Biology·Xin LiGuoxiong Xu

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