Crystallographic structure of the T domain-DNA complex of the Brachyury transcription factor.
Muller, Christoph W.; Herrmann, Bernhard G.
[Letter] Nature. 389(6653):884-888, October 23, 1997.

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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 [1-6]. 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 [7-11]. The T-box encodes a DNA-binding domain of about 180 amino-acid residues, the T domain [12]. Here we report the X-ray structure of the T domain from Xenopus laevis [2] 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.

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