Structure of IRF-1 with bound DNA reveals determinants of interferon regulation

Escalante, Carlos R.; Yie, Junming; Thanos, Dimitris; Aggarwal, Aneel K.

doi:10.1038/34224

Cited by 397interferon and immune responsesGenomics and Chromatin DynamicsEnzyme Structure and Function

Structure of IRF-1 with bound DNA reveals determinants of interferon regulation

Escalante, Carlos R., Yie, Junming, Thanos, Dimitris, Aggarwal, Aneel K.·1998·Nature

DOI 10.1038/34224

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Abstract

The family of interferon regulatory factor (IRF) transcription factors is important in the regulation of interferons in response to infection by virus and in the regulation of interferon-inducible genes. The IRF family is characterized by a unique 'tryptophan cluster' DNA-binding region. Here we report the crystal structure of the IRF-1 region bound to the natural positive regulatory domain I (PRD I) DNA element from the interferon-beta promoter. The structure provides the first three-dimensional view of a member of the growing IRF family, revealing a new helix-turn-helix motif that latches onto DNA through three of the five conserved tryptophans. The motif selects a short GAAA core sequence through an obliquely angled recognition helix, with an accompanying bending of the DNA axis in the direction of the protein. Together, these features suggest a basis for the occurrence of GAAA repeats within IRF response elements and provide clues to the assembly of the higher-order interferon-beta enhancesome.

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The IRF-1-DNA co-crystal structure shows IRF-1 makes extensive contacts with DNA backbone phosphates up to six nucleotides upstream of the GAAA core.
“The recent IRF-1-DNA co-crystal structure (Escalante et al., 1998) reveals that in addition to the specific base contacts made by the recognition helix, IRF-1 makes extensive contacts with DNA backbone phosphates, even as far as six nucleotides upstream of the GAAA recognition core.”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Escalante et al., 1998

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Authors: Escalante, C. R., Yie, J., Thanos, D., & Aggarwal, A. K.
Affiliations: Icahn School of Medicine at Mount Sinai (US)
Columbia University (US)
Corresponding author: Aggarwal, Aneel K.
ORCID: Escalante, Carlos R.
Yie, Junming
Thanos, Dimitris
Aggarwal, Aneel K.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1998-01
Volume: 391
Issue: 6662
Pages: 103-106
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/34224
OpenAlex: W2167065653
Cited by: 397
References: 29
Citations by year: 2026: 9 · 2025: 11 · 2024: 10 · 2023: 12 · 2022: 10 · 2021: 7 · 2020: 21 · 2019: 12 · 2018: 13 · 2017: 21 · 2016: 11 · 2015: 8 · 2014: 14 · 2013: 14 · 2012: 12
FWCI: 8.65
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords: IRF1, interferon regulatory factors, transcription factor-DNA complex, helix-turn-helix motif, interferon-beta promoter, DNA bending, interferon regulation, crystal structure
MeSH terms: Amino Acid Sequence, Binding Sites, DNA, DNA-Binding Proteins, Gene Expression Regulation, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Phosphoproteins, Promoter Regions, Genetic, Protein Conformation, Interferon-beta, Helix-Loop-Helix Motifs, Crystallography, X-Ray, Interferon Regulatory Factor-1

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Structure of IRF-1 with bound DNA reveals determinants of interferon regulation

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