Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Rengachari, S; Groiss, S; Devos, JM; Caron, E; Grandvaux, N; Panne, D.
Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function.
Proc Natl Acad Sci U S A. 2018; 115(4): E601-E609.
Doi: 10.1073/pnas.1718426115
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- Co-authors Med Uni Graz
- Groiss Silvia
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- Abstract:
- 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. Copyright © 2018 the Author(s). Published by PNAS.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Gene Expression Regulation -
- HEK293 Cells -
- Humans -
- Interferon-Stimulated Gene Factor 3, gamma Subunit - genetics
- Interferon-Stimulated Gene Factor 3, gamma Subunit - metabolism
- Janus Kinases - metabolism
- Mice -
- Point Mutation -
- Protein Domains -
- STAT2 Transcription Factor - genetics
- STAT2 Transcription Factor - metabolism
- Signal Transduction -
- Find related publications in this database (Keywords)
- JAK/STAT signaling
- IRF transcription factor
- STAT2
- innate immunity
- crystal structure