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Cited by 91interferon and immune responsesCytokine Signaling Pathways and InteractionsGenomics and Chromatin Dynamics

Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function

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Rengachari, Srinivasan, Groiss, Silvia, Devos, Juliette M., Caron, Elise, Grandvaux, Nathalie, Panne, Daniel·2018·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1718426115PMC PMC5789952

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Abstract

Significance: Cytokines interact with their receptors and activate JAK–STAT signaling pathways that lead to changes in gene expression. In mammals, there are seven STATs that have arisen due to gene duplication and genetic drift. STATs have similar DNA binding specificity, and how individual STATs have subfunctionalized to regulate very specific cytokine responses in cells is poorly understood. Here we describe X-ray structures that show how one STAT family member, STAT2, specifically pairs with a member of the IRF family of transcription factors, IRF9. Despite overall structural similarity among STAT and IRF family members, surface features in the interacting domains of IRF9 and STAT2 have diverged to enable specific interaction between these family members and to enable the antiviral response.

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  • Induced reporter expression is ablated by BAF inhibition, consistent with previous findings that chromatin remodelers are a key component in type I IFN response for both basal and induced expression.

    “Furthermore, induced reporter expression is ablated by BAF inhibition (Fig. S6H), consistent with previous findings that chromatin remodelers are a key component in type I IFN response for both basal and induced expression42”

    From Single-molecule states link transcription factor binding to gene expression (2024) · cites this paper as [42]

    The Results section reports IFNβ-induced reporter activity and its loss with IRF9 mutations, not with BAF inhibition. Searches for BAF, SWI/SNF, and chromatin remodeling found no passage in our copy addressing whether remodelers are required for basal or induced type I IFN expression. (LLM, conf=0.75)

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Authors
Rengachari, S., Groiss, S., Devos, J. M., Caron, E., Grandvaux, N., & Panne, D.
Affiliations
  • European Molecular Biology Laboratory (FR)
  • Centre Hospitalier de l’Université de Montréal (CA)
Corresponding author
Panne, Daniel
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2018-01-09
Volume
115
Issue
4
Pages
E601-E609
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1718426115
PMC
PMC5789952
OpenAlex
W2611222371
Cited by
91
References
2
Citations by year
2026: 10 · 2025: 13 · 2024: 16 · 2023: 4 · 2022: 12 · 2021: 13 · 2020: 7 · 2019: 8 · 2018: 8
FWCI
3.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by-nc-nd)
  • Leicester Research Archive (University of Leicester) (submittedVersion, cc-by-nc-nd)
Funders
  • Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (355306)
  • Fondation ARC pour la Recherche sur le Cancer (20131200682)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
STAT2, IRF9, ISGF3, coiled-coil domain, JAK/STAT signaling, interferon-stimulated genes, protein-protein interaction, crystal structure, STAT1, transcription factor complex
MeSH terms
Protein Domains, Animals, Gene Expression Regulation, Humans, Signal Transduction, Point Mutation, STAT2 Transcription Factor, Interferon-Stimulated Gene Factor 3, gamma Subunit, Mice, Janus Kinases, HEK293 Cells

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