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Methylation of two-component response regulator MtrA in mycobacteria negatively modulates its DNA binding and transcriptional activation

Authors :
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
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.

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