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Methylation of two-component response regulator MtrA in mycobacteria negatively modulates its DNA binding and transcriptional activation
- Source :
- Biochemical Journal
- Publication Year :
- 2020
- Publisher :
- Portland Press Ltd., 2020.
-
Abstract
- Post-translational modifications such as phosphorylation, nitrosylation, and pupylation modulate multiple cellular processes in Mycobacterium tuberculosis. While protein methylation at lysine and arginine residues is widespread in eukaryotes, to date only two methylated proteins in Mtb have been identified. Here, we report the identification of methylation at lysine and/or arginine residues in nine mycobacterial proteins. Among the proteins identified, we chose MtrA, an essential response regulator of a two-component signaling system, which gets methylated on multiple lysine and arginine residues to examine the functional consequences of methylation. While methylation of K207 confers a marginal decrease in the DNA-binding ability of MtrA, methylation of R122 or K204 significantly reduces the interaction with the DNA. Overexpression of S-adenosyl homocysteine hydrolase (SahH), an enzyme that modulates the levels of S-adenosyl methionine in mycobacteria decreases the extent of MtrA methylation. Most importantly, we show that decreased MtrA methylation results in transcriptional activation of mtrA and sahH promoters. Collectively, we identify novel methylated proteins, expand the list of modifications in mycobacteria by adding arginine methylation, and show that methylation regulates MtrA activity. We propose that protein methylation could be a more prevalent modification in mycobacterial proteins.
- Subjects :
- DNA, Bacterial
Arginine
Lysine
Methylation
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Bacterial Proteins
Histone methylation
Protein methylation
Promoter Regions, Genetic
Molecular Biology
030304 developmental biology
0303 health sciences
Chemistry
030302 biochemistry & molecular biology
Promoter
Mycobacterium tuberculosis
Cell Biology
3. Good health
DNA-Binding Proteins
Response regulator
ATP-Binding Cassette Transporters
Protein Processing, Post-Translational
DNA
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 477
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....bbcfcb5c534c49b07498c887f71a1348
- Full Text :
- https://doi.org/10.1042/bcj20200455