| Autor: |
F. Agriesti, MUSIANI, FRANCESCO, C. Del Campo, M. Iurlaro, RONCARATI, DAVIDE, SPARLA, FRANCESCA, CIURLI, STEFANO LUCIANO, DANIELLI, ALBERTO, SCARLATO, VINCENZO |
| Přispěvatelé: |
F. Agriesti, D. Roncarati, F. Musiani, C. Del Campo, M. Iurlaro, F. Sparla, S. Ciurli, A. Danielli, V. Scarlato |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
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| Popis: |
According to the grounding work of Jacob and Monod, transcription factors (TFs) regulate gene expression by modulating their DNA binding affinity in response to a particular signal, or in the presence of a specific cofactor, much akin inducible or repressible on-off switches. Whilst the vast majority of TFs recognize distinct elements through the readout of conserved nucleotide motifs in the major groove of DNA, a few are able to bind specifically in the minor groove. Here we report the finding of a TF able to discriminatively exploit the binding to either the major or the minor DNA groove in order to mediate opposite read-out of the same regulatory signal. This mechanism accounts for the ability of the ferric uptake regulator Fur, a widespread prokaryotic transcriptional regulator involved in metal ion homeostasis and virulence in many bacteria, to repress the expression of both iron-inducible and iron-repressible genes in the human pathogen Helicobacter pylori. In particular, we demonstrate that Fur exploits the two grooves of DNA to function like a molecular commutator switch. In the apo-form, Fur binds with higher affinity to an iron-induced promoter as dimer, through the readout of thymine dimers in the major groove, contributing to its transcriptional repression under iron-deplete conditions. Conversely, on iron-repressed promoters, the metal ion acts as co-repressor, inducing protein conformational changes that prompt multimerization of the regulator and high affinity binding to the minor groove in occurrence of AT-rich inverted repeats. The latter mechanism appears to involve an Arg residue in helix H1 of the HTH-DNA-binding domain. In addition, molecular modelling and in silico docking indicate that binding to the minor groove involves conformation of the HTH-DNA binding domains of four Fur monomers into a tetrameric DNA clamp. These results provide evidence for a novel regulatory mechanism that may be exploited also in other bacteria. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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