vitro.) 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. Although these residues do not directly contact the DNA, they pack against the HTH and this packing is essential for 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. TetR Protein Family As of June 2005, this family of proteins had about 2,353 members that are transcriptional regulators. (Transcriptional regulators control gene expression.) These proteins contain a helix-turn-helix (HTH) motif that is the DNA-binding domain. The second helix is considered to be most important for DNA sequence specificity and often recognizes nucleic acids within the major groove of the double helix. In the majority of the family members, this motif is on the N-terminal end of the protein and is highly conserved. The high conservation of the HTH motif is not observed for the other domains of the protein. The differences observed in these other regulatory domains are likely due to differences in the molecules that each family member senses. TetR protein family members are mostly transcriptional repressors, meaning that they prevent the expression of certain genes at the DNA level. These proteins can act on genes with various functions including antibiotic resistance, biosynthesis and metabolism, bacterial pathogenesis, and response to cell stress. See also Tetracycline controlled transcriptional activation References External links Regulation of Antibiotic Resistance Tetracycline antibiotics