The TetR family of transcriptional regulators is a family of repressors widely distributed in bacteria. Proteins of TetR family control antibiotic and toxic efflux pumps, enzymes involved in different catabolic pathways, antibiotic biosynthesis , virulence and other processes.
This family is characterized by significant amino acid sequence homology extending over a 47-residue stretch constituting the DNA binding domain.
All the TetR proteins fulfil the generalized profile “TetR-profile”. The value obtained after matching with this profile is always above the 8.6 threshold in proteins that belong to the TetR family.
The TetR proteins have a common three-dimensional structure of the DNA-binding domain. This domain corresponds to the stretch defined in the TetR-profile. This DNA-interacting domain includes one Helix-Turn-Helix (H-T-H) motif that interact with the DNA major groove corresponding to the operator
The majority of the proteins of the family are homodimers with two DNA-binding domains and a regulatory domain including a dimerization domain and two drug-binding pockets. There are two crystallized proteins of TetR family:TetR and QacR. Both proteins appear as homodimers in the crystals but the crystal of QacR bound to the operator shows four QacR molecules (two homodimers) by operator.
The functions in which TetR proteins are involved can be grouped schematically in several groups:
1- Regulation of efflux pumps and transporters involved in Antibiotic resistance and toxic tolerance.
2- Regulation of Antibiotic biosynthesis
3- Regulation of enzymes involved in catabolism
4- Biosynthesis of products important for bacteria: osmoprotectants, nucleotides, amino acids, PHAs, protoheme,…
5- Regulation of the differentiation (sporulation, mycelium formation), colony phenotype, biofilm formation.
6- Regulation of genes involved in virulence
7- Regulation of synthesis butyrolactones
8- Butyrolactone or autoinductor receptors
9- Global regulation
10- Others
In TetR family the more frequent function is the regulation of efflux pumps and transporters involved in antibiotic resistance and toxic tolerance. TetR proteins involved in this type of function appear in many prokaryotic genera. TetR, MtrR and AcrR are important proteins with this type of function.
Proteins as HapR and ScmR are implied in virulence and it could be considered that all TetR proteins present in pathogens involved in antibiotic and disinfectants resistance also are involved in pathogenicity.
Considering the functions in which TetR family of transcriptional proteins are involved , it is reasonable to propose these proteins as possible targets for designing a broad spectrum of applications in the fields of biotechnology and medicine.
