Structural Elucidation of Viral Antagonism of Innate Immunity at the STAT1 Interface - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Cell Reports Année : 2019

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

Résumé

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.
Fichier principal
Vignette du fichier
1-s2.0-S2211124719313208-main.pdf (3.59 Mo) Télécharger le fichier
Loading...

Dates et versions

pasteur-02868855 , version 1 (15-06-2020)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

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⟩

Collections

PASTEUR
32 Consultations
103 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More