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Structural basis for DNA bending by the architectural transcription factor LEF-1

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Abstract

LYMPHOID enhancer-binding factor (LEF-1) and the closely related T-cell factor 1 (TCF-1) are sequence-specific and cell-type-specific DNA-binding proteins that play important regulatory roles in organogenesis and thymocyte differentiation1–5. LEF-1 participates in regulation of the enhancer associated with the T cell receptor (TCR)-α gene by inducing a sharp bend in the DNA and facilitating interactions between Ets-1, PEBP2-α, and ATF/ CREB transcription factors bound at sites flanking the LEF-1 site1,2,6,7. It seems that LEF-1 plays an architectural role in the assembly and function of this regulatory nucleoprotein complex7,8. LEF-1 recognizes a specific nucleotide sequence through a high-mobility-group (HMG) domain1,2. Proteins containing HMG domains bind DNA in the minor groove, bend the double helix6,9,10, and recognize four-way junctions and other irregular DNA structures9,11. Here we report the solution structure of a complex of the LEF-1 HMG domain and adjacent basic region with its cognate DNA. The structure reveals the HMG domain bound in the widened minor groove of a markedly distorted and bent double helix. The basic region binds across the narrowed major groove and contributes to DNA recognition.

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Authors and Affiliations

  1. Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, 92037, USA

    John J. Love, Xiang Li, David A. Case & Peter E. Wright

  2. Department of Chemistry and Biochemistry, University of California, San Diego, California, 92037, USA

    John J. Love

  3. Howard Hughes Medical Institute and Departments of Microbiology and Biochemistry, University of California, San Francisco, California, 94143, USA

    Klaus Giese & Rudolf Grosschedl

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  1. John J. Love
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  2. Xiang Li
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  4. Klaus Giese
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  5. Rudolf Grosschedl
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Love, J., Li, X., Case, D. et al. Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature 376, 791–795 (1995). https://doi.org/10.1038/376791a0

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