Systematic Analysis of Mycobacterial Acylation Reveals First Example of Acylation-mediated Regulation of Enzyme Activity of a Bacterial Phosphatase

• Published in: The Journal of biological chemistry 2015-10, Vol.290 (43), p.26218-26234
• Main Authors: Singhal, Anshika, Arora, Gunjan, Virmani, Richa, Kundu, Parijat, Khanna, Tanya, Sajid, Andaleeb, Misra, Richa, Joshi, Jayadev, Yadav, Vikas, Samanta, Sintu, Saini, Neeru, Pandey, Amit K., Visweswariah, Sandhya S., Hentschker, Christian, Becher, Dörte, Gerth, Ulf, Singh, Yogendra
• Format: Article
• Language: English
• Subjects: Acylation; Amino Acid Sequence; bacterial signal transduction; l modifications; mass spectrometry (MS); Microbiology; Molecular Sequence Data; Mycobacterium tuberculosis; Mycobacterium tuberculosis - enzymology; Mycobacterium tuberculosis - metabolism; phosphatase; Phosphoric Monoester Hydrolases - chemistry; Phosphoric Monoester Hydrolases - metabolism; Phosphorylation; post-translation modification; propionylation; protein acylation; Protein Conformation; Sequence Homology, Amino Acid; Structure-Activity Relationship; succinylation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M115.687269

Protein lysine acetylation is known to regulate multiple aspects of bacterial metabolism. However, its presence in mycobacterial signal transduction and virulence-associated proteins has not been studied. In this study, analysis of mycobacterial proteins from different cellular fractions indicated dynamic and widespread occurrence of lysine acetylation. Mycobacterium tuberculosis proteins regulating diverse physiological processes were then selected and expressed in the surrogate host Mycobacterium smegmatis. The purified proteins were analyzed for the presence of lysine acetylation, leading to the identification of 24 acetylated proteins. In addition, novel lysine succinylation and propionylation events were found to co-occur with acetylation on several proteins. Protein-tyrosine phosphatase B (PtpB), a secretory phosphatase that regulates phosphorylation of host proteins and plays a critical role in Mycobacterium infection, is modified by acetylation and succinylation at Lys-224. This residue is situated in a lid region that covers the enzyme's active site. Consequently, acetylation and succinylation negatively regulate the activity of PtpB. Background: Post-translational modifications regulate Mycobacterium tuberculosis physiology and pathogenesis. Results: Several novel signal transduction proteins are regulated by lysine acylation, including the virulence-associated protein-tyrosine phosphatase PtpB. Conclusion:M. tuberculosis lysine acylation-regulated pathways affect other signal transduction modules. Significance: This is the first report of acylation-dependent regulation of enzyme activity of a bacterial phosphatase.