The TetR Family of Regulators

Abstract

SUMMARY The most common prokaryotic signal transduction mechanisms are the one-component systems in which a single polypeptide contains both a sensory domain and a DNA-binding domain. Among the >20 classes of one-component systems, the TetR family of regulators (TFRs) are widely associated with antibiotic resistance and the regulation of genes encoding small-molecule exporters. However, TFRs play a much broader role, controlling genes involved in metabolism, antibiotic production, quorum sensing, and many other aspects of prokaryotic physiology. There are several well-established model systems for understanding these important proteins, and structural studies have begun to unveil the mechanisms by which they bind DNA and recognize small-molecule ligands. The sequences for more than 200,000 TFRs are available in the public databases, and genomics studies are identifying their target genes. Three-dimensional structures have been solved for close to 200 TFRs. Comparison of these structures reveals a common overall architecture of nine conserved α helices. The most important open question concerning TFR biology is the nature and diversity of their ligands and how these relate to the biochemical processes under their control.

A multidrug resistance plasmid contains the molecular switch for type VI secretion in Acinetobacter baumannii

“…Proteins within the H-NS family have been suggested to be involved in T6SS regulation (31,32). TetR-like regulators play a broad role in many aspects of prokaryotic physiology (33), and members of this family have been implicated in T6SS regulation (34). Close homologs of TetR1 and TetR2 are only present in A. baumannii harboring pAB04-1/pAB3-like plasmids.…”

Stress Physiology of Lactic Acid Bacteria

“…OCSs are proteins containing sensory and signaling domains; they lack HK and receptor domains and can be identified by amino acid conservation in their DNA-binding domains and by different conserved motifs (54). Twenty families of major prokaryotic OCSs have been recognized so far (68). With the exception of the MetJ family, they are all represented in LAB.…”

“…TetR proteins constitute a widespread family of OCSs regulating many aspects of bacterial physiology and interacting with a vast array of ligands (68). A small number of TetR family regulators have been characterized for LAB, among which only S. pneumoniae SczA has so far been implicated in a stress response.…”

Engineering Gene Circuits for Mammalian Cell–Based Applications

“…Most prokaryotic regulator proteins consist of an amino-terminal DBD that recognizes a unique DNA operator sequence and a carboxyterminal sensory domain (SD) that specifically binds to a ligand molecule (Fig. 1A) (Cuthbertson and Nodwell 2013). Their diversity and sensory capacity render these proteins attractive for mammalian gene regulation and gene circuit design .…”

“…Prokaryotic regulator protein families are a widespread class of sensor proteins (e.g., .200,000 prokaryotic regulator protein-like sequences have been identified) that enable cells to adapt rapidly to environmental and metabolic changes by controlling the transcription of target genes depending on specific input signals (Ramos et al 2005;Cuthbertson and Nodwell 2013). Most prokaryotic regulator proteins consist of an amino-terminal DBD that recognizes a unique DNA operator sequence and a carboxyterminal sensory domain (SD) that specifically binds to a ligand molecule (Fig.…”