Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP.
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.
Zheng
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Howard Hughes Medical Institute, Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 USA.
Fraenkel
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Pabo
C O
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Pavletich
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NP
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D050684:E2F Transcription Factors; D050704:E2F4 Transcription Factor; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D056465:Retinoblastoma-Binding Protein 1; D017386:Sequence Homology, Amino Acid; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D056465:Retinoblastoma-Binding Protein 1; C094103:TFDP2 protein, human; D050680:Transcription Factor DP1; D014157:Transcription Factors; D004247:DNA