N-Acetyl-l-Glutamate Kinase (NAGK) from Oxygenic Phototrophs: PII Signal Transduction across Domains of Life Reveals Novel Insights in NAGK Control

N-Acetyl-l-glutamate kinase (NAGK) catalyzes the first committed step in arginine biosynthesis in organisms that perform the cyclic pathway of ornithine synthesis. In eukaryotic and bacterial oxygenic phototrophs, the activity of NAGK is controlled by the P_II signal transduction protein. Recent X-ray analysis of NAGK-P_II complexes from a higher plant (Arabidopsis thaliana) and a cyanobacterium (Synechococcus elongatus) revealed that despite several differences, the overall structure of the complex is highly similar. The present study analyzes the functional conservation of P_II-mediated NAGK regulation in plants and cyanobacteria to distinguish between universal properties and those that are specific for the different phylogenetic lineages. This study shows that plant and cyanobacterial P_II proteins can mutually regulate the NAGK enzymes across the domains of life, implying a high selective pressure to conserve P_II-NAGK interaction over more than 1.2 billion years of separate evolution. The non-conserved C-terminus of S. elongatus NAGK was identified as an element, which strongly enhances arginine inhibition and is responsible for most of the differences between S. elongatus and A. thaliana NAGK with respect to arginine sensitivity. Both P_II proteins relieve arginine inhibition of NAGK, and in both lineages, P_II-mediated relief from arginine inhibition is antagonized by 2-oxoglutarate. Together, these properties highlight the conserved role of P_II as a signal integrator of the C/N balance sensed as 2-oxoglutarate to regulate arginine synthesis in oxygenic phototrophs.