Short peptides act as inducers, anti-inducers and corepressors of Tet repressor.

Dagmar Goeke, Daniela Kaspar, Christoph Stoeckle, Sandra Grubmüller, Christian Berens, Marcus Klotzsche, Wolfgang Hillen

Lehrstuhl für Mikrobiologie, Department Biologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91058 Erlangen, Germany.

Journal of molecular biology 2012 Feb 10

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Protein allostery plays a pivotal role in many regulatory processes. Prominent examples are cell-surface receptors, which allosterically transmit ligand-generated signals to their cytoplasmic domains, or bacterial transcription factors, which alternate between a free conformation and a DNA-bound conformation in response to binding an effector molecule. The bacterial transcription factor Tet repressor (TetR) belongs to the latter category and is regarded as highly adapted to tetracyclines (tc's) as effectors. However, peptides isolated in this study were able to trigger distinct allosteric behavior including induction, anti-induction and corepression. Binding of the peptides' C-terminal residues consistently occurs within the tc-binding pocket of TetR. However, an extensive analysis of TetR mutants revealed that inducing and anti-inducing peptides utilize different parts of the binding pocket to elicit their respective regulatory responses. This study demonstrates that even for transcription factors evolved for high effector specificity, alternative molecular structures can exert similar and even novel effects, provided that sufficient chemical diversity and molecular flexibility, as found in peptide libraries, is accompanied by an efficient in vivo selection system. The high number of bioactive peptides and their extensive sequence diversity suggests that switching from small-molecule-controlled transcription regulation to a signal transduction network might be rather easily accomplished. These findings will strongly affect protein-mediated regulation of gene expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

Citation

Dagmar Goeke, Daniela Kaspar, Christoph Stoeckle, Sandra Grubmüller, Christian Berens, Marcus Klotzsche, Wolfgang Hillen. Short peptides act as inducers, anti-inducers and corepressors of Tet repressor. Journal of molecular biology. 2012 Feb 10;416(1):33-45