The Phosphohistidine Phosphatase SixA Targets a Phosphotransferase System

• Published in: mBio Vol. 9; no. 6
• Main Authors: Schulte, Jane E, Goulian, Mark
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 27-11-2018
• Subjects: Carrier Proteins - metabolism; CvrA; Escherichia coli - enzymology; Escherichia coli - genetics; Escherichia coli - growth & development; Escherichia coli - metabolism; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Gene Deletion; Gene Expression Regulation, Bacterial; histidine phosphatase; histidine phosphorylation; Membrane Proteins - metabolism; Metabolic Networks and Pathways - genetics; Molecular Biology and Physiology; Phosphate-Binding Proteins; Phosphoprotein Phosphatases - genetics; Phosphoprotein Phosphatases - metabolism; Phosphotransferases (Nitrogenous Group Acceptor) - metabolism; Protein Kinases - metabolism; PtsN; YcgO; histidine phosphatase; histidine phosphorylation; PtsN; CvrA; YcgO
• ISSN: 2161-2129; 2150-7511
• DOI: 10.1128/mBio.01666-18

SixA, a well-conserved protein found in proteobacteria, actinobacteria, and cyanobacteria, is the only reported example of a bacterial phosphohistidine phosphatase. A single protein target of SixA has been reported to date: the
histidine kinase ArcB. The present work analyzes an ArcB-independent growth defect of a
deletion in
A screen for suppressors, analysis of various mutants, and phosphorylation assays indicate that SixA modulates phosphorylation of the nitrogen-related phosphotransferase system (PTS
). The PTS
is a widely conserved bacterial pathway that regulates diverse metabolic processes through the phosphorylation states of its protein components, EI
, NPr, and EIIA
, which receive phosphoryl groups on histidine residues. However, a mechanism for dephosphorylating this system has not been reported. The results presented here suggest a model in which SixA removes phosphoryl groups from the PTS
by acting on NPr. This work uncovers a new role for the phosphohistidine phosphatase SixA and, through factors that affect SixA expression or activity, may point to additional inputs that regulate the PTS
One common means to regulate protein activity is through phosphorylation. Protein phosphatases exist to reverse this process, returning the protein to the unphosphorylated form. The vast majority of protein phosphatases that have been identified target phosphoserine, phosphotheronine, and phosphotyrosine. A widely conserved phosphohistidine phosphatase was identified in
20 years ago but remains relatively understudied. The present work shows that this phosphatase modulates the nitrogen-related phosphotransferase system, a pathway that is regulated by nitrogen and carbon metabolism and affects diverse aspects of bacterial physiology. Until now, there was no known mechanism for removing phosphoryl groups from this pathway.