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

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

doi:10.1038/34224

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

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

Research output: Contribution to journal › Article › peer-review

345 Scopus citations

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-β 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-β enhancesome.

Original language	English
Pages (from-to)	103-106
Number of pages	4
Journal	Nature
Volume	391
Issue number	6662
DOIs	https://doi.org/10.1038/34224
State	Published - 1 Jan 1998

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title = "Structure of IRF-1 with bound DNA reveals determinants of interferon regulation",

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-β 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-β enhancesome.",

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AU - Escalante, Carlos R.

AU - Yie, Junming

AU - Thanos, Dimitris

AU - Aggarwal, Aneel K.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - 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-β 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-β enhancesome.

AB - 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-β 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-β enhancesome.

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

Abstract

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