4V2F: Tetracycline Repressor Tetr(d), Unliganded

Genes that render bacteria resistant to tetracycline-derived antibiotics are tightly regulated by repressors of the TetR family. In their physiologically relevant, magnesium-complexed form, tetracyclines induce allosteric rearrangements in the TetR homodimer, leading to its release from the promoter and derepression of transcription. According to earlier crystallographic work, recognition of the tetracycline-associated magnesium ion by TetR is crucial and triggers the allosteric cascade. Nevertheless, the derivative 5a,6-anhydrotetracycline, which shows an increased affinity for TetR, causes promoter release even in the absence of magnesium. To resolve this paradox, it has been proposed that metal-free 5a,6-anhydrotetracycline acts via an exceptional, conformationally different induction mode that circumvents the normal magnesium requirement. We have tested this hypothesis by determining crystal structures of TetR-5a,6-anhydrotetracycline complexes in the presence of magnesium, ethylenediaminetetraacetic acid, or high concentrations of potassium. Analysis of these three structures reveals that, irrespective of the metal, the effects of 5a,6-anhydrotetracycline binding are indistinguishable from those of canonical induction by other tetracyclines. Together with a close scrutiny of the earlier evidence of a metal-triggered mechanism, these results demonstrate that magnesium recognition per se is not a prerequisite for tetracycline repressor allostery.
PDB ID: 4V2FDownload
MMDB ID: 125509
PDB Deposition Date: 2014/10/9
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 4V2F: dimeric; determined by author and by software (PISA)
Molecular Components in 4V2F
Label Count Molecule
Proteins (2 molecules)
Tetracycline Repressor Protein Class D(Gene symbol: tetR)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB