5oen

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Crystal Structure of STAT2 in complex with IRF9

Structural highlights

5oen is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[IRF9_MOUSE] Transcription factor that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. IRF9/ISGF3G associates with the phosphorylated STAT1:STAT2 dimer to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state.

Publication Abstract from PubMed

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.

Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function.,Rengachari S, Groiss S, Devos JM, Caron E, Grandvaux N, Panne D Proc Natl Acad Sci U S A. 2018 Jan 9. pii: 1718426115. doi:, 10.1073/pnas.1718426115. PMID:29317535^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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 Jan 9. pii: 1718426115. doi:, 10.1073/pnas.1718426115. PMID:29317535 doi:http://dx.doi.org/10.1073/pnas.1718426115