Structural insight into LexA–RecA* interaction

RecA protein is a hallmark for the bacterial response to insults inflicted on DNA. It catalyzes the strand exchange step of homologous recombination and stimulates self-inactivation of the LexA transcriptional repressor. Importantly, by these activities, RecA contributes to the antibiotic resistance...

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Autores principales: Kovačič, Lidija, Paulič, Nejc, Leonardi, Adrijana, Hodnik, Vesna, Anderluh, Gregor, Podlesek, Zdravko, Žgur-Bertok, Darja, Križaj, Igor, Butala, Matej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834820/
https://www.ncbi.nlm.nih.gov/pubmed/23965307
http://dx.doi.org/10.1093/nar/gkt744
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author Kovačič, Lidija
Paulič, Nejc
Leonardi, Adrijana
Hodnik, Vesna
Anderluh, Gregor
Podlesek, Zdravko
Žgur-Bertok, Darja
Križaj, Igor
Butala, Matej
author_facet Kovačič, Lidija
Paulič, Nejc
Leonardi, Adrijana
Hodnik, Vesna
Anderluh, Gregor
Podlesek, Zdravko
Žgur-Bertok, Darja
Križaj, Igor
Butala, Matej
author_sort Kovačič, Lidija
collection PubMed
description RecA protein is a hallmark for the bacterial response to insults inflicted on DNA. It catalyzes the strand exchange step of homologous recombination and stimulates self-inactivation of the LexA transcriptional repressor. Importantly, by these activities, RecA contributes to the antibiotic resistance of bacteria. An original way to decrease the acquisition of antibiotic resistance would be to block RecA association with LexA. To engineer inhibitors of LexA–RecA complex formation, we have mapped the interaction area between LexA and active RecA–ssDNA filament (RecA*) and generated a three-dimensional model of the complex. The model revealed that one subunit of the LexA dimer wedges into a deep helical groove of RecA*, forming multiple interaction sites along seven consecutive RecA protomers. Based on the model, we predicted that LexA in its DNA-binding conformation also forms a complex with RecA* and that the operator DNA sterically precludes interaction with RecA*, which guides the induction of SOS gene expression. Moreover, the model shows that besides the catalytic C-terminal domain of LexA, its N-terminal DNA-binding domain also interacts with RecA*. Because all the model-based predictions have been confirmed experimentally, the presented model offers a validated insight into the critical step of the bacterial DNA damage response.
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spelling pubmed-38348202013-11-21 Structural insight into LexA–RecA* interaction Kovačič, Lidija Paulič, Nejc Leonardi, Adrijana Hodnik, Vesna Anderluh, Gregor Podlesek, Zdravko Žgur-Bertok, Darja Križaj, Igor Butala, Matej Nucleic Acids Res Structural Biology RecA protein is a hallmark for the bacterial response to insults inflicted on DNA. It catalyzes the strand exchange step of homologous recombination and stimulates self-inactivation of the LexA transcriptional repressor. Importantly, by these activities, RecA contributes to the antibiotic resistance of bacteria. An original way to decrease the acquisition of antibiotic resistance would be to block RecA association with LexA. To engineer inhibitors of LexA–RecA complex formation, we have mapped the interaction area between LexA and active RecA–ssDNA filament (RecA*) and generated a three-dimensional model of the complex. The model revealed that one subunit of the LexA dimer wedges into a deep helical groove of RecA*, forming multiple interaction sites along seven consecutive RecA protomers. Based on the model, we predicted that LexA in its DNA-binding conformation also forms a complex with RecA* and that the operator DNA sterically precludes interaction with RecA*, which guides the induction of SOS gene expression. Moreover, the model shows that besides the catalytic C-terminal domain of LexA, its N-terminal DNA-binding domain also interacts with RecA*. Because all the model-based predictions have been confirmed experimentally, the presented model offers a validated insight into the critical step of the bacterial DNA damage response. Oxford University Press 2013-11 2013-08-21 /pmc/articles/PMC3834820/ /pubmed/23965307 http://dx.doi.org/10.1093/nar/gkt744 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Kovačič, Lidija
Paulič, Nejc
Leonardi, Adrijana
Hodnik, Vesna
Anderluh, Gregor
Podlesek, Zdravko
Žgur-Bertok, Darja
Križaj, Igor
Butala, Matej
Structural insight into LexA–RecA* interaction
title Structural insight into LexA–RecA* interaction
title_full Structural insight into LexA–RecA* interaction
title_fullStr Structural insight into LexA–RecA* interaction
title_full_unstemmed Structural insight into LexA–RecA* interaction
title_short Structural insight into LexA–RecA* interaction
title_sort structural insight into lexa–reca* interaction
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834820/
https://www.ncbi.nlm.nih.gov/pubmed/23965307
http://dx.doi.org/10.1093/nar/gkt744
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