9srw
Cryo-EM structure of the Mlc tetramer in complex with the anti-repressor MtfA
Structural highlights
FunctionMTFA_ECOLI Involved in the modulation of the activity of the glucose-phosphotransferase system (glucose-PTS) (PubMed:16855233). Interacts with the transcriptional repressor Mlc, preventing its interaction with DNA and leading to the modulation of expression of genes regulated by Mlc, including ptsG, which encodes the PTS system glucose-specific EIICB component (PubMed:16855233, PubMed:22178967).[1] [2] Shows zinc-dependent metallopeptidase activity (By similarity). In vitro, can cleave several artificial substrates (PubMed:22178967). The greatest activity and specificity is observed for L-alanine fused to 4-nitroanilide (L-alanine-pNA) (PubMed:22178967). Shows significantly lower activity towards L-arginine-pNA, L-proline-pNA, hippuryl-L-phenylalanine and hippuryl-L-arginine, and cannot use FTC-casein (PubMed:22178967). Mlc does not appear to be a biologically relevant peptidase substrate (PubMed:22178967). Biologically relevant targets may have a function in growth transition under changing environmental conditions (PubMed:22178967).[UniProtKB:A6TB83][3] Publication Abstract from PubMedThe 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(Glc), 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. Structural basis of Mlc-mediated transcriptional regulation of carbohydrate metabolism.,Roth P, Fender I, Jeckelmann JM, Ucurum Z, Lemmin T, Fotiadis D Nat Commun. 2026 Jul 11. doi: 10.1038/s41467-026-75270-8. PMID:42436118[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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