Crystallographic structure of the T domain-DNA complex of the Brachyury transcription factor.
The mouse Brachyury (T) gene is the prototype of a growing family of so-called T-box genes which encode transcriptional regulators and have been identified in a variety of invertebrates and vertebrates, including humans. Mutations in Brachyury and other T-box genes result in drastic embryonic phenotypes, indicating that T-box gene products are essential in tissue specification, morphogenesis and organogenesis. The T-box encodes a DNA-binding domain of about 180 amino-acid residues, the T domain. Here we report the X-ray structure of the T domain from Xenopus laevis in complex with a 24-nucleotide palindromic DNA duplex. We show that the protein is bound as a dimer, interacting with the major and the minor grooves of the DNA. A new type of specific DNA contact is seen, in which a carboxy-terminal helix is deeply embedded into an enlarged minor groove without bending the DNA. Hydrophobic interactions and an unusual main-chain carbonyl contact to a guanine account for sequence-specific recognition in the minor groove by this helix. Thus the structure of this T domain complex with DNA reveals a new way in which a protein can recognize DNA.
Müller
C W
CW
European Molecular Biology Laboratory, Grenoble Outstation, France. mueller@embl-grenoble.fr
Herrmann
B G
BG
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D005326:Fetal Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism; D014982:Xenopus laevis; D000098908:Brachyury Protein
D004247:DNA; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D011994:Recombinant Proteins; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein