A Comprehensive Analysis of Structural and Sequence Conservation in the TetR Family Transcriptional Regulators

Zhou, Yu; Reichheld, Sean E.; Savchenko, Alexei; Parkinson, John; Davidson, Alan R.

doi:10.1016/j.jmb.2010.05.062

Cited by 127 publications

(208 citation statements)

References 62 publications

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“…RamR is a TetR family regulator that binds to an operator sequence in the upstream region of ramA (Chinni et al, 2010). TetR family regulators are homodimeric DNA-binding proteins (Yu et al, 2010) that are composed of an N-terminal DNA-binding domain and a C-terminal domain that mediates dimerization and binds to substrates (Yu et al, 2010). Thus, it is hypothesized that indole binds to the C-terminal domain of RamR and derepresses the transcriptional activity of ramA by causing detachment from the binding site of RamR.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat

et al. 2011

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Salmonella enterica serovar Typhimurium has at least nine multidrug efflux pumps. Among these, AcrAB is constitutively expressed and is the most efficient, playing a role in both drug resistance and virulence. The acrAB locus is induced by indole, Escherichia coli-conditioned medium, and bile salts. This induction is dependent on RamA through the binding sequence in the upstream region of acrA that binds RamA. In the present study, we made a detailed investigation of the ramA and acrAB induction mechanisms in Salmonella in response to indole, a biological oxidant for bacteria. We found that acrAB and ramA induction in response to indole is dependent on RamR. However, the cysteine residues of RamR do not play a role in the induction of ramA in response to indole, and the oxidative effect of indole is therefore not related to ramA induction via RamR. Furthermore, we showed that paraquat, a superoxide generator, induces acrAB but not ramA. We further discovered that the mechanism of acrAB induction in response to paraquat is dependent on SoxS. The data indicate that there are at least two independent induction pathways for acrAB in response to extracellular signals such as indole and paraquat. We propose that Salmonella utilizes these regulators for acrAB induction in response to extracellular signals in order to adapt itself to environmental conditions.

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Section: Discussionmentioning

confidence: 99%

Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat

et al. 2011

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“…Although these TFRs bind different ligands (many structurally unrelated compounds such as ethidium, proflavin, and rhodamine 6G for AcrR (36), saturated fatty acid-CoA and unsaturated fatty acid-CoA for DesT (39,40), and numerous structurally dissimilar monovalent and bivalent cationic and lipophilic compounds for QacR (41,42)), their ligand-binding cavities are similarly positioned in the ligand-binding domain (28). Ligand binding results in a conformational change of the DNA-binding domain, for which the relocation of ␣6 helix upon ligand binding induces a pendulum-like motion of the DNA-binding domain in TFRs including TetR (43), QacR (41), and DesT (39).…”

Section: Discussionmentioning

confidence: 99%

“…The global fold of HrtR is similar to that of TetR family transcriptional regulators (TFRs) that possess nine conserved helices, within which helices 1-3 comprise the DNA-binding domain and helices 4 -9 comprise the ligand-binding domain (27,28). In addition to the nine conserved helices, HrtR possesses extra short helices (␣ N and ␣ C shown in Fig.…”

Section: Heme-responsive Regulation For Dna Binding Of Hrtr-tomentioning

confidence: 99%

Structural Basis for the Transcriptional Regulation of Heme Homeostasis in Lactococcus lactis

Sawai

Yamanaka

Sugimoto

et al. 2012

Journal of Biological Chemistry

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“…In addition, a4-a9 was observed to consist of a six-helix bundle structure, and RamR may recognize a substrate in this region. It was previously suggested that the central triangle (a5-a7) is conserved in the C-terminus structure of TetR family regulators 19 . However, we found that this central triangle was not conserved in RamR because of its tortuosity in a7 (Fig.…”

Section: Structure Of the Ramr Proteinmentioning

confidence: 99%

The crystal structure of multidrug-resistance regulator RamR with multiple drugs

et al. 2013

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RamR is a transcriptional repressor of the gene-encoding RamA protein, which controls the expression of the multidrug efflux system genes acrAB-tolC. RamR is an important multidrug-resistance factor, however, its structure and the identity of the molecules to which it responds have been unknown. Here, we report the crystal structure of RamR in complex with multiple drugs, including berberine, crystal violet, dequalinium, ethidium bromide and rhodamine 6G. All compounds are found to interact with Phe155 of RamR, and each compound is surrounded by different amino acid residues. Binding of these compounds to RamR reduces its DNA-binding affinity, which results in the increased expression of ramA. Our results reveal significant flexibility in the substrate-recognition region of RamR, which regulates the bacterial efflux participating in multidrug resistance.

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A Comprehensive Analysis of Structural and Sequence Conservation in the TetR Family Transcriptional Regulators

Cited by 127 publications

References 62 publications

Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat

Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat

Structural Basis for the Transcriptional Regulation of Heme Homeostasis in Lactococcus lactis

The crystal structure of multidrug-resistance regulator RamR with multiple drugs

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