Structural Elucidation of Viral Antagonism of Innate Immunity at the STAT1 Interface.
Cell Rep
; 29(7): 1934-1945.e8, 2019 11 12.
Article
em En
| MEDLINE
| ID: mdl-31722208
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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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Lyssavirus
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Fator de Transcrição STAT1
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Imunidade Inata
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article