Methylation of two-component response regulator MtrA in mycobacteria negatively modulates its DNA binding and transcriptional activation
| Autor: | Parijat Kundu, Richa Misra, Saba Naz, Yogendra Singh, Andaleeb Sajid, Ulf Gerth, Ankita Dabla, Anshika Singhal, Suresh Kumar, Virginie Molle, Mohita Gaur, Kriti Sharma, Gunjan Arora, Vinay Kumar Nandicoori, Richa Virmani, Jacob Nellissery, Anand Swaroop |
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| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Biochemical Journal |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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