Structural basis for DNA bending by the architectural transcription factor LEF-1.
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.
Love
J J
JJ
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Li
X
X
Case
D A
DA
Giese
K
K
Grosschedl
R
R
Wright
P E
PE
D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli; D051538:Hepatocyte Nuclear Factor 1-alpha; D006609:High Mobility Group Proteins / Q000737:chemistry; D051821:Lymphoid Enhancer-Binding Factor 1; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D006609:High Mobility Group Proteins; C496488:Hnf1a protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011994:Recombinant Proteins; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors; D004247:DNA