Signal transduction to the Azotobacter vinelandii NIFL-NIFA regulatory system is influenced directly by interaction with 2-oxoglutarate and the PII regulatory protein

PII-like signal transduction proteins, which respond to the nitrogen status via covalent modification and signal the carbon status through the binding of 2-oxoglutarate, have been implicated in the regulation of nitrogen fixa tion in several diazotrophs. The NIFL-NIFA two-component regulatory system, which integrates metabolic signals to fine-tune regulation of nitrogenase synthesis in Azotobacter vinelandii, is a potential target for PII-mediated signal transduction. Here we demonstrate that the inhibitory activity of t he A. vinelandii NIFL protein is stimulated by interaction with the non-uri dylylated form of PII-like regulatory proteins. We also observe that the NI FL-NIFA system is directly responsive to 2-oxoglutarate. We propose that th e PII protein signals the nitrogen status by interaction with the NIFL-NIFA system under conditions of nitrogen excess, and that the inhibitory activi ty of NIFL is relieved by elevated levels of 2-oxoglutarate when PII is uri dylylated under conditions of nitrogen limitation. Our observations suggest a model for signal transduction to the NIFL-NIFA system in response to car bon and nitrogen status which is clearly distinct from that suggested from studies on other diazotrophs.