Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function.pdf (2.17 MB)
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Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function

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journal contribution
posted on 26.04.2018, 13:12 by S. Rengachari, S. Groiss, J. M. Devos, E. Caron, N. Grandvaux, Daniel Panne
Cytokine signaling through the JAK/STAT pathway controls multiple cellular responses including growth, survival, differentiation, and pathogen resistance. An expansion in the gene regulatory repertoire controlled by JAK/STAT signaling occurs through the interaction of STATs with IRF transcription factors to form ISGF3, a complex that contains STAT1, STAT2, and IRF9 and regulates expression of IFN-stimulated genes. ISGF3 function depends on selective interaction between IRF9, through its IRF-association domain (IAD), with the coiled-coil domain (CCD) of STAT2. Here, we report the crystal structures of the IRF9-IAD alone and in a complex with STAT2-CCD. Despite similarity in the overall structure among respective paralogs, the surface features of the IRF9-IAD and STAT2-CCD have diverged to enable specific interaction between these family members. We derive a model for the ISGF3 complex bound to an ISRE DNA element and demonstrate that the observed interface between STAT2 and IRF9 is required for ISGF3 function in cells.

History

Citation

Proceedings of the National Academy of Sciences, 2018, 115 (4), E601-E609

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/Biological Sciences/Molecular & Cell Biology

Version

VoR (Version of Record)

Published in

Proceedings of the National Academy of Sciences

Publisher

National Academy of Sciences

issn

0027-8424

eissn

1091-6490

Acceptance date

06/12/2017

Copyright date

2018

Available date

26/04/2018

Publisher version

http://www.pnas.org/content/115/4/E601

Language

en