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

Nature. 1995 Aug 31;376(6543):791-5. doi: 10.1038/376791a0.


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 differentiation. LEF-1 participates in regulation of the enhancer associated with the T cell receptor (TCR)-alpha gene by inducing a sharp bend in the DNA and facilitating interactions between Ets-1, PEBP2-alpha, and ATF/CREB, transcription factors bound at sites flanking the LEF-1 site. It seems that LEF-1 plays an architectural role in the assembly and function of this regulatory nucleoprotein complex. LEF-1 recognizes a specific nucleotide sequence through a high-mobility-group (HMG) domain. Proteins containing HMG domains bind DNA in the minor groove, bend the double helix, and recognize four-way junctions and other irregular DNA structures. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA / chemistry*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • Escherichia coli
  • Hepatocyte Nuclear Factor 1-alpha
  • High Mobility Group Proteins / chemistry
  • Lymphoid Enhancer-Binding Factor 1
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Nucleic Acid Conformation
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Sequence Alignment
  • T Cell Transcription Factor 1
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics


  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 1-alpha
  • High Mobility Group Proteins
  • Hnf1a protein, mouse
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Recombinant Proteins
  • T Cell Transcription Factor 1
  • Transcription Factors
  • DNA