Figure 1. The mode of interaction of Cro repressor with DNA inferred from the original crystal structure of the protein. In the figure only the backbone of the protein is shown (solid lines). Two subunits of the protein are related by a horizontal 2-fold axis of symmetry, labelled Q. The amino-terminus of the subunits are respectively labelled N_O and N_B. Each Cro subunit contains a helix-turn-helix, with the second helix occupying a major groove of the DNA. (From Anderson WF, Ohlendorf DH, Takeda Y and Matthews BW (1981) Structure of the cro repressor from bacteriophage 8 and its interaction with DNA. Nature 290: 754–758. Reproduced by permission of Nature Publishing Group.)

Figure 2. The result of a search among the amino acid sequences of DNA-binding proteins for those with apparent correspondence to the helix-turn-helix region (i.e. the ₂–₃ region) of Cro repressor of phage ( Cro). The symbols above the first row indicate the location of that residue in Cro: Open circles indicate external residues with side-chains fully exposed to solvent; half-filled circles indicate surface residues partly exposed to solvent; solid circles indicate internal buried residues; stars indicate residues presumed to interact with DNA. A greater amount of underlining indicates a greater degree of sequence conservation at that position among the 10 sequences being compared. (From Ohlendorf et al., 1983.)

Figure 3. Figure illustrating the general arrangement of the helix-turn-helix unit (labelled ₂-₃) in a number of gene-regulatory proteins. The figure on the left is a side view with a 2-fold axis in the plane of the paper. The view on the right is looking along the 2-fold axis (diad symbol in the middle of the figure). The two helix-turn-helix units are related by the 2-fold axis of symmetry. The 2-fold symmetry also applies, at least approximately, to the DNA.

Figure 4. Comparison of the complexes of the cI repressor and Cro proteins from phage bound to operator DNA. In each case the recognition helix is shown in red. (a) and (c) Two views at right angles of the headpiece of cI repressor bound to DNA. The recognition helices are aligned perpendicular to the long axis of the DNA and are tilted so that only the amino-terminal end of the recognition helix occupies the major groove. (b) and (d) Corresponding views of Cro bound to operator DNA. In this case the recognition helix lies along the major groove and is aligned parallel to it. (From Albright and Matthews, 1998.)

Figure 5. Schematic illustration of the multitude of interactions that occur in a typical interaction between a DNA regulatory protein and its operator site on DNA. The example shown is one half of the overall complex between Cro protein and its operator. The DNA is shown diagrammatically with circles corresponding to phosphate groups and rectangles corresponding to the four possible bases (A, adenine; C, cytosine; T, thymine; G, guanine). The arrows show hydrogen-bonding contacts between the protein and the DNA; dashed lines show nonpolar contacts. Bases or phosphates that are contacted are darkened. Amino acids numbered between 14 and 35 come from the helix-turn-helix motif; the other amino acid contacts come from other parts of the protein. (Adapted from Albright and Matthews, 1998)