9.B.321.  The Actinobacterial Nutrient-sensing Signal Transduction Pathway Controlling Glutamate Metabolism (SigT) Family 

Nutrients stimulate phosphorylation of the protein kinase G (PknG) substrate, GarA, in Mycobacterium smegmatis and Mycobacterium tuberculosis. The action of GarA in regulating central metabolism depends upon whether it is phosphorylated. Bhattacharyya et al. 2018 revealed the mechanism by which nutrients activate PknG. Two genes were identified as co-conserved and co-expressed with the pknG gene. Their products are a lipoprotein, GlnH, and a transmembrane protein, GlnX. They showed that GlnX is functionally linked to PknG activation, and the ligand specificity of GlnH proved to match the amino acids that stimulate GarA phosphorylation. The structures of GlnH in complex with different amino acid ligands (aspartate, glutamate, and asparagine) were determined. It was proposed that the amino acid concentration in the periplasm is sensed by GlnH, and that protein-protein interactions allow transmission of this information across the membrane via GlnX to activate PknG. This sensory system would allow regulation of nutrient utilization in response to changes in nutrient availability.

The sensor, signaling, and effector proteins are conserved throughout the Actinobacteria, including the human pathogen Mycobacterium tuberculosis, the industrial amino acid producer Corynebacterium glutamicum, and the antibiotic-producing Streptomyces species (Bhattacharyya et al. 2018).




Bhattacharyya, N., I.N. Nkumama, Z. Newland-Smith, L.Y. Lin, W. Yin, R.E. Cullen, J.S. Griffiths, A.R. Jarvis, M.J. Price, P.Y. Chong, R. Wallis, and H.M. O'Hare. (2018). An Aspartate-Specific Solute-Binding Protein Regulates Protein Kinase G Activity To Control Glutamate Metabolism in Mycobacteria. MBio 9:.


TC#NameOrganismal TypeExample

Signal transduction pathway involved a periplasmic receptor, probably a lipoprotein, GlnH, specific for at least 3 amino acids, glu, asp and gln, a transmembrane protein with 5 TMSs, GlnX, and a cytoplasmic protein kinase, PknG that phosphorylates a trascriptional regulator, GarA (Bhattacharyya et al. 2018).

Four constituent signal transduction pathway of Mycobacterium tuberculosis


Homologues of TC# 9.B.321.1.1 including the transmembrane protein, GlnX (TAG98393), the kinase, KpnG (TAG98397), and the transcriptional regulator phosphorylated by PknG, GarA (TAG98394), all within a single gene cluster.  The other proteins within this cluster are also included under this TC#.  These include (1) a VWA domain-containing protein of 0 TMSs with similarity to E-ClC family members (TC# 1.A.13; TAG98395; 426 aas; 0 TMSs), a zinc ribbon domain-containing protein of 324 aas and 0 TMSs (like TC# 9.B.250.1.4) and a DedA protein (like TC#9.B.27.2.4) of 207 aas and 5 or 6 TMSs (TAG98398).

Homologues of TC# 9.B.321.1.1 in Oscillatoriales cyanobacterium