Journal article

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

Md Alamgir Hossain, Florence Larrous, Stephen M Rawlinson, Jingyu Zhan, Ashish Sethi, Youssef Ibrahim, Maria Aloi, Kim G Lieu, Yee-Foong Mok, Michael DW Griffin, Naoto Ito, Toyoyuki Ose, Herve Bourhy, Gregory W Moseley, Paul R Gooley

Cell Reports | CELL PRESS | Published : 2019

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, wi..

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Grants

Awarded by Australian Research Council


Awarded by National Health and Medical Research Council


Awarded by Japanese Society for the Promotion of Science


Funding Acknowledgements

We thank Cassandra David for assistance with tissue culture, the Monash Micro Imaging facility (Monash University), and the nuclear magnetic resonance facility (University of Melbourne; Australian Research Council equipment grant LE120100022). This work was supported by National Health and Medical Research Council grant 1125704 to G.W.M., P.R.G., and H.B. and grants 1160838, 1079211, and 1003244 to G.W.M., and Australian Research Council grant DP150102569 to G.W.M.; a Grimwade Fellowship provided by the Meigunyah Fund to G.W.M.; and Japanese Society for the Promotion of Science fellowships S11102 and L14563 to G.W.M.