TetR Regulators: A Structural and Functional Perspective

Hussain Bhukya, Ruchi Anand

Research output: Contribution to journalReview ArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Tetracycline repressor family of transcription regulators (TetR-FTRs) is one of the most predominant families of transcription factors in the prokaryotic system. Classically, they are associated with antimicrobial resistance since they regulate the genes encoding the efflux pumps that export antibiotics out of the cell. Analysis shows that TetR-FTRs adopt a broader role in bacterial function than earlierly envisioned. Apart from efflux of antibiotics these proteins also regulate pathways associated with cell-cell signaling, antibiotic biosynthesis, biofilm formation, etc. Furthermore, an in-depth scrutiny of the available three-dimensional structures of TetR-FTRs and comparison of their various forms (apo, liganded and DNA-bound) helped to obtain valuable insights into the underlying molecular mechanism of action. TetR-FTRs possess a modular architecture with the N-terminal DNA-binding domain comprising canonical DNA-binding helix-turn-helix motif that is mostly conserved, whereas, the C-terminal signal reception domain is evolutionarily more diverse as it is tailored to accept the appropriate ligand. The TetR-FTRs serve as repressors when bound to their target DNA sequence, in the absence of their signaling molecule. On ligand binding, de-repression occurs by the coordinated motions of helices at the interface of the two domains. The DNA-binding domain undergoes a pendulum-like shift along the connecting helix, α4, and this motion transmits the signal. Overall, an understanding of the allosteric mechanism allows these proteins to switch from one state to another, an important transformation of their regulatory function.

Original languageEnglish
Pages (from-to)245-259
Number of pages15
JournalJournal of the Indian Institute of Science
Volume97
Issue number2
DOIs
Publication statusPublished - 1 Jun 2017
Externally publishedYes

Keywords

  • Allostery
  • Antimicrobial resistance
  • CprB
  • DNA binding
  • Quorum sensing
  • Streptomyces
  • TetR
  • Tetracycline repressor

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