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| Title | Structural basis of Mlc-mediated transcriptional regulation of carbohydrate metabolism. |
|---|---|
| Journal, issue, pages | Nat Commun, Year 2026 |
| Publish date | Sep 25, 2025 |
Authors | Patrick Roth / Inken Fender / Jean-Marc Jeckelmann / Zöhre Ucurum / Thomas Lemmin / Dimitrios Fotiadis / ![]() |
| PubMed Abstract | The global transcriptional repressor Mlc of Escherichia coli regulates genes involved in carbohydrate transport and metabolism, particularly glucose uptake via the glucose-specific phosphotransferase ...The global transcriptional repressor Mlc of Escherichia coli regulates genes involved in carbohydrate transport and metabolism, particularly glucose uptake via the glucose-specific phosphotransferase system (PTS). Unlike conventional repressors, Mlc exemplifies a system in which interactions with diverse macromolecules govern its activity. Here, we present cryo-electron microscopy structures of Mlc alone and in complexes with regulatory partners, including the glucose-specific PTS transporter IICB, a cognate DNA operator and the anti-repressor MtfA, capturing multiple assemblies central to transcription control. These structures reveal the molecular architecture of Mlc and its interactions with binding partners. Together with molecular dynamics simulations, they provide insights into the structural dynamics of these complexes. Our findings establish the structural basis of membrane-transporter involvement in transcriptional regulation, the mechanism of anti-repressor action and DNA recognition. This work provides a structural framework for understanding bacterial transcriptional regulation across diverse systems. |
External links | Nat Commun / PubMed:42436118 |
| Methods | EM (single particle) |
| Resolution | 2.3 - 2.96 Å |
| Structure data | ![]()
EMDB-55151: Focussed refinement of the Mlc tetramer ![]()
EMDB-55152: Focused refinement of Mlc tetramer EMDB-55153, PDB-9srt: ![]()
EMDB-55154: Consensus reconstruction of Mlc tetramer in complex with ptsG operator DNA ![]()
EMDB-55155: Focused reconstruction of Mlc tetramer in complex with ptsG operator DNA EMDB-55156, PDB-9sru: ![]()
EMDB-55157: Consensus reconstruction of the Mlc tetramer in complex with the anti-repressor MtfA ![]()
EMDB-55158: Focused reconstruction of the Mlc tetramer in complex with the anti-repressor MtfA ![]()
EMDB-55159: Focused reconstruction of the Mlc tetramer in complex with the anti-repressor MtfA EMDB-55160, PDB-9srw: ![]()
EMDB-55161: Consensus reconstruction of the Mlc tetramer in complex with the glucose-specific IICB transporter ![]()
EMDB-55162: Focused reconstruction of the Mlc tetramer in complex with the glucose-specific IICB transporter ![]()
EMDB-55163: Focused reconstruction of the Mlc tetramer in complex with the glucose-specific IICB transporter ![]()
EMDB-55164: Focused reconstruction of the Mlc tetramer in complex with the glucose-specific IICB transporter EMDB-55165, PDB-9srx: |
| Chemicals | ![]() ChemComp-ZN: ![]() ChemComp-BGC: |
| Source |
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Keywords | DNA BINDING PROTEIN / Repressor / DNA-binding protein / tetramer / transcription regulation / gene regulation / carbohydrate utilization / metal-binding / DNA / operator / anti-repressor / Metalloprotease / Hydrolase / membrane transporter / glucose / transmembrane protein / membrane-tethering |
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