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...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2013
|
Materias: | |
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 |
_version_ | 1782292049851056128 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3834820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kovaciclidija structuralinsightintolexarecainteraction AT paulicnejc structuralinsightintolexarecainteraction AT leonardiadrijana structuralinsightintolexarecainteraction AT hodnikvesna structuralinsightintolexarecainteraction AT anderluhgregor structuralinsightintolexarecainteraction AT podlesekzdravko structuralinsightintolexarecainteraction AT zgurbertokdarja structuralinsightintolexarecainteraction AT krizajigor structuralinsightintolexarecainteraction AT butalamatej structuralinsightintolexarecainteraction |