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TitleStructural basis of Mlc-mediated transcriptional regulation of carbohydrate metabolism.
Journal, issue, pagesNat Commun, Year 2026
Publish dateSep 25, 2025
AuthorsPatrick Roth / Inken Fender / Jean-Marc Jeckelmann / Zöhre Ucurum / Thomas Lemmin / Dimitrios Fotiadis /
PubMed AbstractThe 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 linksNat Commun / PubMed:42436118
MethodsEM (single particle)
Resolution2.3 - 2.96 Å
Structure data


EMDB Unreleased entry

EMDB-55151: Focussed refinement of the Mlc tetramer
Method: EM (single particle) / Resolution: 2.62 Å


EMDB Unreleased entry

EMDB-55152: Focused refinement of Mlc tetramer
Method: EM (single particle) / Resolution: 2.89 Å

55153
EMDB Unreleased entry

EMDB-55153, PDB-9srt:
Cryo-EM structure of the Mlc tetramer
Method: EM (single particle) / Resolution: 2.74 Å


EMDB Unreleased entry

EMDB-55154: Consensus reconstruction of Mlc tetramer in complex with ptsG operator DNA
Method: EM (single particle) / Resolution: 2.47 Å


EMDB Unreleased entry

EMDB-55155: Focused reconstruction of Mlc tetramer in complex with ptsG operator DNA
Method: EM (single particle) / Resolution: 2.56 Å

55156
EMDB Unreleased entry

EMDB-55156, PDB-9sru:
Cryo-EM structure of Mlc in complex with ptsG operator DNA
Method: EM (single particle) / Resolution: 2.47 Å


EMDB Unreleased entry

EMDB-55157: Consensus reconstruction of the Mlc tetramer in complex with the anti-repressor MtfA
Method: EM (single particle) / Resolution: 2.3 Å


EMDB Unreleased entry

EMDB-55158: Focused reconstruction of the Mlc tetramer in complex with the anti-repressor MtfA
Method: EM (single particle) / Resolution: 2.3 Å


EMDB Unreleased entry

EMDB-55159: Focused reconstruction of the Mlc tetramer in complex with the anti-repressor MtfA
Method: EM (single particle) / Resolution: 2.94 Å

55160
EMDB Unreleased entry

EMDB-55160, PDB-9srw:
Cryo-EM structure of the Mlc tetramer in complex with the anti-repressor MtfA
Method: EM (single particle) / Resolution: 2.3 Å


EMDB Unreleased entry

EMDB-55161: Consensus reconstruction of the Mlc tetramer in complex with the glucose-specific IICB transporter
Method: EM (single particle) / Resolution: 2.96 Å


EMDB Unreleased entry

EMDB-55162: Focused reconstruction of the Mlc tetramer in complex with the glucose-specific IICB transporter
Method: EM (single particle) / Resolution: 2.78 Å


EMDB Unreleased entry

EMDB-55163: Focused reconstruction of the Mlc tetramer in complex with the glucose-specific IICB transporter
Method: EM (single particle) / Resolution: 2.95 Å


EMDB Unreleased entry

EMDB-55164: Focused reconstruction of the Mlc tetramer in complex with the glucose-specific IICB transporter
Method: EM (single particle) / Resolution: 2.81 Å

55165
EMDB Unreleased entry

EMDB-55165, PDB-9srx:
Cryo-EM structure of the Mlc repressor in complex with the glucose-specific IICB transporter
Method: EM (single particle) / Resolution: 2.96 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-BGC:
beta-D-glucopyranose

Source
  • escherichia coli (E. coli)
KeywordsDNA 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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