TetR

TetR is a transcriptional repressor that regulates the tetracycline resistance operon in bacteria, most notably the tetR-tetA arrangement found on plasmids and transposons such as Tn10. It is a homodimeric DNA-binding protein with each subunit containing an N-terminal helix-turn-helix motif that recognizes a palindromic operator sequence (tetO) and a C-terminal regulatory domain that binds tetracycline-like compounds.

In the absence of tetracycline, TetR binds to tetO and represses transcription of the adjacent tetA gene, which encodes a tetracycline efflux pump, thereby limiting resistance gene expression. When tetracycline or related antibiotics such as doxycycline binds to TetR, the repressor undergoes a conformational change that reduces its affinity for tetO, causing it to dissociate from DNA and permitting transcription of tetA and other TetR-regulated genes.

The tetR gene is typically located next to tetA and encodes a protein around 200 amino acids in length; TetR family members form dimers and share a common architecture that supports versatile ligand sensing and DNA recognition. The TetR family includes numerous homologs with varied ligand specificities, contributing to diverse regulatory networks in bacteria.

In molecular biology, TetR-based systems are widely used as inducible transcription factors. In practice, Tet-Off and Tet-On configurations employ TetR-family repressors to control gene expression in response to tetracycline or its analogs, particularly doxycycline, enabling tightly regulated expression in bacteria and, with engineered variants, in eukaryotic cells. TetR remains a fundamental model for understanding allosteric regulation of DNA-binding proteins and antibiotic resistance control.