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

Nature volume 391, pages 103–106 (1998)Cite this article

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 genes1,2. 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-β promoter1. 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-β enhancesome.

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Figure 1: a, At the top is shown the sequence of the IFN-β promoter containing the regulatory elements PRD I-IV (ref. 1).
Figure 2: An overview of the IRF-1–DNA complex.
Figure 3: Protein–DNA interactions.
Figure 4: A model showing the van der Waals surfaces of the DNA-binding regions of IRF-1 and the NF-κB p50 homodimer bound to the PRD I and.

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Acknowledgements

We thank the staff at CHESS for facilitating data collection, E. Jacobson, H. Viadiu and D. Wah for help with data collection, G. Mogilnitskiy for technical assistance, L. Shapiro and H. Weinstein for comments on the manuscript. Coordinates have been deposited in the Brookhaven Protein Database. Accession number 1IF1.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Structural Biology Program, Box 1677, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, 10029, New York, USA

    Carlos R. Escalante & Aneel K. Aggarwal

  2. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, 10032, New York, USA

    Junming Yie & Dimitris Thanos

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  1. Carlos R. Escalante
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  2. Junming Yie
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  4. Aneel K. Aggarwal
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Correspondence to Aneel K. Aggarwal.

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Escalante, C., Yie, J., Thanos, D. et al. Structure of IRF-1 with bound DNA reveals determinants of interferon regulation. Nature 391, 103–106 (1998). https://doi.org/10.1038/34224

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