3ZQF

Structure of Tetracycline repressor in complex with antiinducer peptide-TAP1

Summary for 3ZQF

• Entry DOI: 10.2210/pdb3zqf/pdb
• Related: 1A6I 1BJ0 1BJY 1BJZ 1DU7 1ORK 1QPI 2TCT 2TRT 2VKE 2VKV 2X6O 2X9D 2XB5 2XGC 2XGD 2XGE 2XPS 2XPT 2XPU 2XPV 2XPW 2XRL 3ZQG 3ZQH 3ZQI
• Descriptor: TETRACYCLINE REPRESSOR PROTEIN CLASS B FROM TRANSPOSON TN10, TETRACYCLINE REPRESSOR PROTEIN CLASS D, ANTI-INDUCER PEPTIDE TAP1 (3 entities in total)
• Functional Keywords: transcription, tetracycline repressor, tetr, inducers, peptidic effectors, allostery
• Biological source: ESCHERICHIA COLI; More
• Total number of polymer chains: 2
• Total formula weight: 25191.60

Authors

Sevvana, M.,Goeke, D.,Stoeckle, C.,Kaspar, D.,Grubmueller, S.,Goetz, C.,Wimmer, C.,Berens, C.,Klotzsche, M.,Muller, Y.A.,Hillen, W. (deposition date: 2011-06-09, release date: 2011-12-28, Last modification date: 2023-12-20)

Primary citation

Sevvana, M.,Goetz, C.,Goeke, D.,Wimmer, C.,Berens, C.,Hillen, W.,Muller, Y.A.
An Exclusive Alpha/Beta Code Directs Allostery in Tetr-Peptide Complexes.
J.Mol.Biol., 416:46-, 2012

PubMed Abstract: The allosteric mechanism of one of the best characterized bacterial transcription regulators, tetracycline repressor (TetR), has recently been questioned. Tetracycline binding induces cooperative folding of TetR, as suggested by recent unfolding studies, rather than switching between two defined conformational states, namely a DNA-binding-competent conformation and a non-DNA-binding conformation. Upon ligand binding, a host of near-native multiconformational structures collapse into a single, highly stabilized protein conformation that is no longer able to bind DNA. Here, structure-function studies performed with four synthetic peptides that bind to TetR and mimic the function of low-molecular-weight effectors, such as tetracyclines, provide new means to discriminate between different allosteric models. Whereas two inducing peptides bind in an extended β-like conformation, two anti-inducing peptides form an α-helix in the effector binding site of TetR. This exclusive bimodal interaction mode coincides with two distinct overall conformations of TetR, namely one that is identical with induced TetR and one that mirrors the DNA-bound state of TetR. Urea-induced unfolding studies show no increase in thermodynamic stability for any of the peptide complexes, although fluorescence measurements demonstrate peptide binding to TetR. This strongly suggests that, at least for these peptide effectors, a classical two-state allosteric model best describes TetR function.

PubMed: 22178479
DOI: 10.1016/J.JMB.2011.12.008

Experimental method

X-RAY DIFFRACTION (2.56 Å)