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).