The solution structure of the human ETS1-DNA complex reveals a novel mode of binding and true side chain intercalation.
The solution structure of a 24.4 kDa specific complex of the DNA-binding domain (DBD) of the human ETS1 (hETS1) oncoprotein with a 17-mer DNA has been solved by NMR. The interaction of the hETS1 DBD with DNA reveals a surprising twist on the general features of helix-turn-helix (HTH)-DNA interactions. Major groove recognition involves the C-terminal two thirds of the HTH recognition helix, while minor groove recognition occurs via true intercalation of the side chain of Trp-28, which extends from the minor to the major groove. This results in a sharp kink of approximately 60 degrees and a widening of the minor groove over one-half turn of the DNA. The orientation of the HTH element of the hETS1 DBD with respect to the major groove is significantly rotated relative to other HTH proteins. These observations establish the ETS family of DNA-binding proteins as a distinct family of HTH proteins.
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
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Werner
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Clore
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Fisher
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Fisher
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Trinh
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Shiloach
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Gronenborn
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019077:Helix-Turn-Helix Motifs; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D012996:Solutions; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012996:Solutions; D014157:Transcription Factors; D014364:Tryptophan; D004247:DNA