The TetR Family of Transcriptional Repressors

Abstract

We have developed a general profile for the proteins of the TetR family of repressors. The stretch that best defines the profile of this family is made up of 47 amino acid residues that correspond to the helix-turn-helix DNA binding motif and adjacent regions in the three-dimensional structures of TetR, QacR, CprB, and EthR, four family members for which the function and three-dimensional structure are known. We have detected a set of 2,353 nonredundant proteins belonging to this family by screening genome and protein databases with the TetR profile. Proteins of the TetR family have been found in 115 genera of gram-positive, α-, β-, and γ-proteobacteria, cyanobacteria, and archaea. The set of genes they regulate is known for 85 out of the 2,353 members of the family. These proteins are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity. The regulatory network in which the family member is involved can be simple, as in TetR (i.e., TetR bound to the target operator represses tetA transcription and is released in the presence of tetracycline), or more complex, involving a series of regulatory cascades in which either the expression of the TetR family member is modulated by another regulator or the TetR family member triggers a cell response to react to environmental insults. Based on what has been learned from the cocrystals of TetR and QacR with their target operators and from their three-dimensional structures in the absence and in the presence of ligands, and based on multialignment analyses of the conserved stretch of 47 amino acids in the 2,353 TetR family members, two groups of residues have been identified. One group includes highly conserved positions involved in the proper orientation of the helix-turn-helix motif and hence seems to play a structural role. The other set of less conserved residues are involved in establishing contacts with the phosphate backbone and target bases in the operator. Information related to the TetR family of regulators has been updated in a database that can be accessed at www.bactregulators.org

Targeting Antibiotic Resistance

“…The expression of this protein is regulated by the Tet repressor (TetR), which binds to the DNA and prevents the transcription of tetA 201. When tetracycline binds to TetR with the aid of Mg 2+ (Figure 44), such as when it binds to its ribosomal target, the conformation of TetR changes and transcription of the resistance genes take place 199, 201, 202…”

Homeostasis and Catabolism of Choline and Glycine Betaine: Lessons from Pseudomonas aeruginosa

“…BetI is a member of the TetR family of transcriptional repressors that bind palindromic sequences as homodimers and are generally involved in resistance to antimicrobials and stress, including osmotic stress (88). Detection of GB by GbdR mediates the transcriptional response involved in GB catabolism (56,67) (Fig.…”

Crystal structure of the transcriptional regulator Rv1219c of Mycobacterium tuberculosis

“…16 This is evident through protein sequence alignment that residues 7-60 of Rv1219c possess 25%, 24%, and 31% amino acid identity to TetR, 17 QacR, 18 and Rv3066, 14 respectively. In addition, superimposition of the Ca atoms of this N-terminal region, between residues 7 and 60, with those of AcrR 19 and Rv3066 14 results in overall rms deviations of 3.1 and 3.2 Å .…”