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Structure-based molecular characterization and regulatory mechanism of the LftR transcription factor from Listeria monocytogenes: Conformational flexibilities and a ligand-induced regulatory mechanism

Listeria monocytogenes is a foodborne pathogen that causes listeriosis and can lead to serious clinical problems, such as sepsis and meningitis, in immunocompromised patients and neonates. Due to a growing number of antibiotic-resistant L. monocytogenes strains, listeriosis can steadily become refra...

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Autores principales: Lee, Choongdeok, Kim, Meong Il, Park, Jaewan, Hong, Minsun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457526/
https://www.ncbi.nlm.nih.gov/pubmed/30970033
http://dx.doi.org/10.1371/journal.pone.0215017
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author Lee, Choongdeok
Kim, Meong Il
Park, Jaewan
Hong, Minsun
author_facet Lee, Choongdeok
Kim, Meong Il
Park, Jaewan
Hong, Minsun
author_sort Lee, Choongdeok
collection PubMed
description Listeria monocytogenes is a foodborne pathogen that causes listeriosis and can lead to serious clinical problems, such as sepsis and meningitis, in immunocompromised patients and neonates. Due to a growing number of antibiotic-resistant L. monocytogenes strains, listeriosis can steadily become refractory to antibiotic treatment. To develop novel therapeutics against listeriosis, the drug resistance mechanism of L. monocytogenes needs to be determined. The transcription factor LftR from L. monocytogenes regulates the expression of a putative multidrug resistance transporter, LieAB, and belongs to the PadR-2 subfamily of the PadR family. Despite the functional significance of LftR, our molecular understanding of the transcriptional regulatory mechanism for LftR and even for the PadR-2 subfamily is highly limited. Here, we report the crystal structure of LftR, which forms a dimer and protrudes two winged helix-turn-helix motifs for DNA recognition. Structure-based mutational and comparative analyses showed that LftR interacts with operator DNA through a LftR-specific mode as well as a common mechanism used by the PadR family. Moreover, the LftR dimer harbors one intersubunit cavity in the center of the dimeric structure as a putative ligand-binding site. Finally, conformational flexibilities in the LftR dimer and in the cavity suggest that a ligand-induced regulatory mechanism would be used by the LftR transcription factor.
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spelling pubmed-64575262019-05-03 Structure-based molecular characterization and regulatory mechanism of the LftR transcription factor from Listeria monocytogenes: Conformational flexibilities and a ligand-induced regulatory mechanism Lee, Choongdeok Kim, Meong Il Park, Jaewan Hong, Minsun PLoS One Research Article Listeria monocytogenes is a foodborne pathogen that causes listeriosis and can lead to serious clinical problems, such as sepsis and meningitis, in immunocompromised patients and neonates. Due to a growing number of antibiotic-resistant L. monocytogenes strains, listeriosis can steadily become refractory to antibiotic treatment. To develop novel therapeutics against listeriosis, the drug resistance mechanism of L. monocytogenes needs to be determined. The transcription factor LftR from L. monocytogenes regulates the expression of a putative multidrug resistance transporter, LieAB, and belongs to the PadR-2 subfamily of the PadR family. Despite the functional significance of LftR, our molecular understanding of the transcriptional regulatory mechanism for LftR and even for the PadR-2 subfamily is highly limited. Here, we report the crystal structure of LftR, which forms a dimer and protrudes two winged helix-turn-helix motifs for DNA recognition. Structure-based mutational and comparative analyses showed that LftR interacts with operator DNA through a LftR-specific mode as well as a common mechanism used by the PadR family. Moreover, the LftR dimer harbors one intersubunit cavity in the center of the dimeric structure as a putative ligand-binding site. Finally, conformational flexibilities in the LftR dimer and in the cavity suggest that a ligand-induced regulatory mechanism would be used by the LftR transcription factor. Public Library of Science 2019-04-10 /pmc/articles/PMC6457526/ /pubmed/30970033 http://dx.doi.org/10.1371/journal.pone.0215017 Text en © 2019 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lee, Choongdeok
Kim, Meong Il
Park, Jaewan
Hong, Minsun
Structure-based molecular characterization and regulatory mechanism of the LftR transcription factor from Listeria monocytogenes: Conformational flexibilities and a ligand-induced regulatory mechanism
title Structure-based molecular characterization and regulatory mechanism of the LftR transcription factor from Listeria monocytogenes: Conformational flexibilities and a ligand-induced regulatory mechanism
title_full Structure-based molecular characterization and regulatory mechanism of the LftR transcription factor from Listeria monocytogenes: Conformational flexibilities and a ligand-induced regulatory mechanism
title_fullStr Structure-based molecular characterization and regulatory mechanism of the LftR transcription factor from Listeria monocytogenes: Conformational flexibilities and a ligand-induced regulatory mechanism
title_full_unstemmed Structure-based molecular characterization and regulatory mechanism of the LftR transcription factor from Listeria monocytogenes: Conformational flexibilities and a ligand-induced regulatory mechanism
title_short Structure-based molecular characterization and regulatory mechanism of the LftR transcription factor from Listeria monocytogenes: Conformational flexibilities and a ligand-induced regulatory mechanism
title_sort structure-based molecular characterization and regulatory mechanism of the lftr transcription factor from listeria monocytogenes: conformational flexibilities and a ligand-induced regulatory mechanism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457526/
https://www.ncbi.nlm.nih.gov/pubmed/30970033
http://dx.doi.org/10.1371/journal.pone.0215017
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