The DNA-binding domains of TetR recognize a 15 base pair palindromic sequence  of the TetA operator. These domains mainly consist of a helix-turn-helix (HTH) motif that is common in TetR protein family members (see below). However, the N-terminal residues preceding this motif have also been shown to be important for DNA binding.
The HTH motifs have mostly hydrophobic interactions with major grooves of the target DNA. Binding of TetR to its target DNA sequence causes changes in both the DNA and TetR. TetR causes widening of the major grooves as well as kinking of the DNA; one helix of the HTH motif of TetR adopts a 310 helical turn as the result of complex DNA interactions.