Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F–DP

  1. Ning Zheng,
  2. Ernest Fraenkel,
  3. Carl O. Pabo, and
  4. Nikola P. Pavletich
  1. Howard Hughes Medical Institute, Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA

Abstract

The E2F and DP protein families form heterodimeric transcription factors that play a central role in the expression of cell cycle-regulated genes. The crystal structure of an E2F4–DP2–DNA complex shows that the DNA-binding domains of the E2F and DP proteins both have a fold related to the winged-helix DNA-binding motif. Recognition of the central c/gGCGCg/c sequence of the consensus DNA-binding site is symmetric, and amino acids that contact these bases are conserved among all known E2F and DP proteins. The asymmetry in the extended binding site TTTc/gGCGCc/g is associated with an amino-terminal extension of E2F4, in which an arginine binds in the minor groove near the TTT stretch. This arginine is invariant among E2Fs but not present in DPs. E2F4 and DP2 interact through an extensive protein–protein interface, and structural features of this interface suggest it contributes to the preference for heterodimers over homodimers in DNA binding.

Keywords

Footnotes

  • Present address: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138 USA.

  • These authors contributed equally to this work.

  • Corresponding author.

  • E-MAIL nikola{at}xray2.mskcc.org; FAX (212) 717-3135.

    • Received January 12, 1999.
    • Accepted January 22, 1999.
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