Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function.
Proc Natl Acad Sci U S A
; 115(4): E601-E609, 2018 01 23.
Article
em En
| MEDLINE
| ID: mdl-29317535
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.
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Base de dados:
MEDLINE
Assunto principal:
Fator de Transcrição STAT2
/
Fator Gênico 3 Estimulado por Interferon, Subunidade gama
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article