Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism
Abstract The Escherichia coli TetR-related transcriptional regulator RutR is involved in the coordination of pyrimidine and purine metabolism. Here we report that lysine acetylation modulates RutR function. Applying the genetic code expansion concept, we produced site-specifically lysine-acetylated...
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Nature Portfolio
2024-02-01
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Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-024-46039-8 |
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author | Magdalena Kremer Sabrina Schulze Nadja Eisenbruch Felix Nagel Robert Vogt Leona Berndt Babett Dörre Gottfried J. Palm Jens Hoppen Britta Girbardt Dirk Albrecht Susanne Sievers Mihaela Delcea Ulrich Baumann Karin Schnetz Michael Lammers |
author_facet | Magdalena Kremer Sabrina Schulze Nadja Eisenbruch Felix Nagel Robert Vogt Leona Berndt Babett Dörre Gottfried J. Palm Jens Hoppen Britta Girbardt Dirk Albrecht Susanne Sievers Mihaela Delcea Ulrich Baumann Karin Schnetz Michael Lammers |
author_sort | Magdalena Kremer |
collection | DOAJ |
description | Abstract The Escherichia coli TetR-related transcriptional regulator RutR is involved in the coordination of pyrimidine and purine metabolism. Here we report that lysine acetylation modulates RutR function. Applying the genetic code expansion concept, we produced site-specifically lysine-acetylated RutR proteins. The crystal structure of lysine-acetylated RutR reveals how acetylation switches off RutR-DNA-binding. We apply the genetic code expansion concept in E. coli in vivo revealing the consequences of RutR acetylation on the transcriptional level. We propose a model in which RutR acetylation follows different kinetic profiles either reacting non-enzymatically with acetyl-phosphate or enzymatically catalysed by the lysine acetyltransferases PatZ/YfiQ and YiaC. The NAD+-dependent sirtuin deacetylase CobB reverses enzymatic and non-enzymatic acetylation of RutR playing a dual regulatory and detoxifying role. By detecting cellular acetyl-CoA, NAD+ and acetyl-phosphate, bacteria apply lysine acetylation of transcriptional regulators to sense the cellular metabolic state directly adjusting gene expression to changing environmental conditions. |
first_indexed | 2024-03-07T14:51:14Z |
format | Article |
id | doaj.art-23d1a0b42fe14e67aa42c7c445204f48 |
institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-03-07T14:51:14Z |
publishDate | 2024-02-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Nature Communications |
spelling | doaj.art-23d1a0b42fe14e67aa42c7c445204f482024-03-05T19:38:49ZengNature PortfolioNature Communications2041-17232024-02-0115112510.1038/s41467-024-46039-8Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolismMagdalena Kremer0Sabrina Schulze1Nadja Eisenbruch2Felix Nagel3Robert Vogt4Leona Berndt5Babett Dörre6Gottfried J. Palm7Jens Hoppen8Britta Girbardt9Dirk Albrecht10Susanne Sievers11Mihaela Delcea12Ulrich Baumann13Karin Schnetz14Michael Lammers15Institute of Biochemistry, University of CologneInstitute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of GreifswaldInstitute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of GreifswaldInstitute of Biochemistry, Department of Biophysical Chemistry, University of GreifswaldInstitute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of GreifswaldInstitute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of GreifswaldInstitute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of GreifswaldInstitute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of GreifswaldInstitute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of GreifswaldInstitute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of GreifswaldInstitute of Microbiology, Department of Microbial Physiology and Molecular Biology, University of GreifswaldInstitute of Microbiology, Department of Microbial Physiology and Molecular Biology, University of GreifswaldInstitute of Biochemistry, Department of Biophysical Chemistry, University of GreifswaldInstitute of Biochemistry, University of CologneInstitute for Genetics, University of Cologne Zülpicher Straße 47aInstitute of Biochemistry, Department of Synthetic and Structural Biochemistry, University of GreifswaldAbstract The Escherichia coli TetR-related transcriptional regulator RutR is involved in the coordination of pyrimidine and purine metabolism. Here we report that lysine acetylation modulates RutR function. Applying the genetic code expansion concept, we produced site-specifically lysine-acetylated RutR proteins. The crystal structure of lysine-acetylated RutR reveals how acetylation switches off RutR-DNA-binding. We apply the genetic code expansion concept in E. coli in vivo revealing the consequences of RutR acetylation on the transcriptional level. We propose a model in which RutR acetylation follows different kinetic profiles either reacting non-enzymatically with acetyl-phosphate or enzymatically catalysed by the lysine acetyltransferases PatZ/YfiQ and YiaC. The NAD+-dependent sirtuin deacetylase CobB reverses enzymatic and non-enzymatic acetylation of RutR playing a dual regulatory and detoxifying role. By detecting cellular acetyl-CoA, NAD+ and acetyl-phosphate, bacteria apply lysine acetylation of transcriptional regulators to sense the cellular metabolic state directly adjusting gene expression to changing environmental conditions.https://doi.org/10.1038/s41467-024-46039-8 |
spellingShingle | Magdalena Kremer Sabrina Schulze Nadja Eisenbruch Felix Nagel Robert Vogt Leona Berndt Babett Dörre Gottfried J. Palm Jens Hoppen Britta Girbardt Dirk Albrecht Susanne Sievers Mihaela Delcea Ulrich Baumann Karin Schnetz Michael Lammers Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism Nature Communications |
title | Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism |
title_full | Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism |
title_fullStr | Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism |
title_full_unstemmed | Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism |
title_short | Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism |
title_sort | bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism |
url | https://doi.org/10.1038/s41467-024-46039-8 |
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