The Antennapedia homeodomain-DNA complex

The structure of the complex of Antennapedia homeodomain and a 14 base pair double stranded operator DNA was solved by nuclear magnetic resonance [4,5] (PDB accession code 1AHD), and recently by X-ray crystallography [6].

The ``$\alpha$-strand'' (GAAAGCCATTAGAG) is numbered from 1 to 14 in 5' to 3' direction. Its complementary ``$\beta$-strand'' (CTCTAATGGCTTTC) is numbered according to the base pair number of the $\alpha$-strand from 14 to 1 from 5' end to 3' end. The base pairs contacted by the homeodomain are typeset in baldface.

  

Figure 1.2: The initial structure of the wild type complex interface. The recognition helix, and the five base pairs of the DNA are shown. The four side chains are indicated: Ile47 (yellow), Gln50 (blue), Asn51 (red), and Met54 (white). The DNA bases are shown without sugars. $\alpha$-strand: C6 and C7 (dark orange), A8, T9 and T10 (red). $\beta$-strand: A10, A9 and T8 (gray), and G7 and G6 (black).

The homeodomain interacts with 6 base pairs of the DNA (CCATTA in the $\alpha$-strand) by its four residues of the recognition helix, Ile47, Gln50, Asn51 and Met54, and by Arg5 of the N-terminal arm, which serves as a connection to the rest of the homeoprotein. Arg5 reaches into the minor groove of the DNA and contacts thymine 11 of the $\beta$-strand (TAATGG) according to the above notation. The rest of the mentioned residues reach into the major groove. Ile47 contacts thymine 8 and adenine 9 (TAATGG) of the $\beta$-strand. Asn51, which is strictly conserved among all homeodomains, hydrogen-bonds to adenine 10 (TAATGG, $\beta$-strand) according to the NMR structure and to adenine 9 (TAATGG, $\beta$-strand) according to the X-ray crystallography, whereas Met54 forms a hydrophobic contact to cytosine 7 (CCATTA) of the $\alpha$-strand. Gln50 hydrogen-bonds to cytosine 7 (CCATTA, $\alpha$-strand) and thymine 8 (TAATGG, $\beta$-strand) as the NMR structure indicates. Both structures show the presence of water molecules in the interface, some of which mediate protein-DNA contacts by hydrogen-bonding to both macromolecules.