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Molecular mechanisms of regulation by a β-alanine-responsive Lrp-type transcription factor from Acidianus hospitalis.
- Source :
-
MicrobiologyOpen [Microbiologyopen] 2023 Jun; Vol. 12 (3), pp. e1356. - Publication Year :
- 2023
-
Abstract
- The leucine-responsive regulatory protein (Lrp) family of transcriptional regulators is widespread among prokaryotes and especially well-represented in archaea. It harbors members with diverse functional mechanisms and physiological roles, often linked to the regulation of amino acid metabolism. BarR is an Lrp-type regulator that is conserved in thermoacidophilic Thermoprotei belonging to the order Sulfolobales and is responsive to the non-proteinogenic amino acid β-alanine. In this work, we unravel molecular mechanisms of the Acidianus hospitalis BarR homolog, Ah-BarR. Using a heterologous reporter gene system in Escherichia coli, we demonstrate that Ah-BarR is a dual-function transcription regulator that is capable of repressing transcription of its own gene and activating transcription of an aminotransferase gene, which is divergently transcribed from a common intergenic region. Atomic force microscopy (AFM) visualization reveals a conformation in which the intergenic region appears wrapped around an octameric Ah-BarR protein. β-alanine causes small conformational changes without affecting the oligomeric state of the protein, resulting in a relief of regulation while the regulator remains bound to the DNA. This regulatory and ligand response is different from the orthologous regulators in Sulfolobus acidocaldarius and Sulfurisphaera tokodaii, which is possibly explained by a distinct binding site organization and/or by the presence of an additional C-terminal tail in Ah-BarR. By performing site-directed mutagenesis, this tail is shown to be involved in ligand-binding response.<br /> (© 2023 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)
- Subjects :
- Transcription Factors metabolism
Alanine metabolism
Ligands
Leucine-Responsive Regulatory Protein genetics
Leucine-Responsive Regulatory Protein metabolism
beta-Alanine
Escherichia coli genetics
Escherichia coli metabolism
DNA, Intergenic
Gene Expression Regulation, Bacterial
Bacterial Proteins genetics
Transcription, Genetic
Acidianus genetics
Acidianus metabolism
Escherichia coli Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-8827
- Volume :
- 12
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- MicrobiologyOpen
- Publication Type :
- Academic Journal
- Accession number :
- 37379425
- Full Text :
- https://doi.org/10.1002/mbo3.1356