Bacterial Ntr nitrogen-regulatory cascade and assimilation output

The bacterial nitrogen-regulatory (Ntr) system, which couples intracellular nitrogen status to the sigma-54-dependent nitrogen-scavenging regulon. The bifunctional uridylyltransferase/uridylyl-removing enzyme GlnD senses glutamine and sets the uridylylation state of the PII signal transduction proteins (GlnB, GlnK). PII proteins also bind 2-oxoglutarate, ATP and ADP, and in their unmodified state stimulate the phosphatase and inhibit the kinase activity of the sensor histidine kinase NtrB. NtrB phosphorylates the conserved receiver aspartate of NtrC, and phosphorylated NtrC uses its AAA+ enhancer-binding module with the sigma-54 holoenzyme to open -24/-12 promoters, inducing ammonium scavenging and ammonia assimilation. The module covers glutamine sensing, PII signal integration, His->Asp phosphotransfer, sigma-54-dependent activation, and the immediate assimilatory output.

The Ntr cascade is conserved across proteobacteria. E. coli K-12, where GlnD, GlnB, GlnK, NtrB and NtrC were defined biochemically, supplies the canonical exemplars; Pseudomonas putida KT2440, whose single PII protein is GlnK, is a second exemplar, and sigma-54 is also exemplified by Nitratidesulfovibrio vulgaris RpoN (a deltaproteobacterial ortholog). The taxon context is kept at Bacteria because PII proteins, GlnD and NtrB/NtrC-type systems are found widely beyond proteobacteria, though partner sets vary. GlnD is now a member: it is the glutamine sensor whose uridylylation of PII is the first step of the cascade. Sigma-54 is included as the output partner of NtrC rather than as a member of the phosphorelay, since a single sigma-54 serves many unrelated enhancer-binding proteins. The wider NtrC-dependent regulon (Nac, urease, nitrate and further nitrogen-source catabolism) and the GS-GOGAT cycle beyond glutamine synthetase are outside this boundary; that cycle is MODULE:bacterial_ammonia_assimilation. PII control of glutamine synthetase through the GlnE adenylyltransferase is also left out, as GlnE is not modelled here. PANTHER families of every member have family reviews (PTHR47320, PTHR30115, PTHR43065, PTHR32071, PTHR32248, PTHR43029, PTHR43407); members are grounded on the subfamily that carries the role, because the whole families are broader: PTHR43065 and PTHR32071 hold many unrelated two-component sensors and enhancer-binding proteins, and NtrB regulation is not expected of archaeal PII (PTHR30115:SF13), so the PII role is given separately for GlnB (SF11) and GlnK (SF20). The NtrB/NtrC relay is a simple two-component system with no histidine-phosphotransfer tier; it declares conformance to MODULE:two_component_relay WITH_DEVIATIONS, as that template prescribes, and the resulting tier/topology advisories are expected.