Structural Elucidation of Viral Antagonism of Innate Immunity at the STAT1 Interface - Institut Pasteur Access content directly
Journal Articles Cell Reports Year : 2019

Structural Elucidation of Viral Antagonism of Innate Immunity at the STAT1 Interface

Abstract

To evade immunity, many viruses express interferon antagonists that target STAT transcription factors as a major component of pathogenesis. Because of a lack of direct structural data, these interfaces are poorly understood. We report the structural analysis of full-length STAT1 binding to an interferon antagonist of a human pathogenic virus. The interface revealed by transferred cross-saturation NMR is complex, involving multiple regions in both the viral and cellular proteins. Molecular mapping analysis, combined with biophysical characterization and in vitro/in vivo functional assays, indicates that the interface is significant in disease caused by a pathogenic field-strain lyssavirus, with critical roles for contacts between the STAT1 coiled-coil/DNA-binding domains and specific regions within the viral protein. These data elucidate the potentially complex nature of IFN antagonist/STAT interactions, and the spatial relationship of protein interfaces that mediate immune evasion and replication, providing insight into how viruses can regulate these essential functions via single multifunctional proteins.
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pasteur-02868855 , version 1 (15-06-2020)

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Attribution - NonCommercial - NoDerivatives

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Md Alamgir Hossain, Florence Larrous, Stephen Rawlinson, Jingyu Zhan, Ashish Sethi, et al.. Structural Elucidation of Viral Antagonism of Innate Immunity at the STAT1 Interface. Cell Reports, 2019, 29 (7), pp.1934-1945.e8. ⟨10.1016/j.celrep.2019.10.020⟩. ⟨pasteur-02868855⟩

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