The PII family comprises a group of widely distributed signal transduction proteins found in nearly all Bacteria and also present in Archaea and in the chloroplasts of Algae and plants. PII form barrel-like homotrimers with a flexible loop, namely T-loop, emerging from each subunit. PII proteins have extraordinary sensory properties; they can exist in a vast range of structural status accordingly to the levels of ATP, ADP and 2-oxogluratate. These metabolites interact allosterically with PII in three conservedbinding sites located in the lateral cavity between each PII subunit. ATP and ADP bind competitively to the nucleotide binding whereas the 2-oxoglutarate only interacts with PII in the presence of MgATP. In Proteobacteria, PII proteins are also subject to a cycle of reversible posttranslational modification. Under a low nitrogen regime, the low intracellular glutamine level triggers the uridylyl-transferase activity of the bi-functional GlnD enzyme promoting the uridylylation of a conserved Tyr-51 located at the top the PII T-loop. Conversely, under a high nitrogen regime, accumulation of intracellular glutamine triggers the uridylyl-removing activity of GlnD and PII accumulates in its non-modified form. The ability of PII to sense important metabolites and integrate signals deriving from energy status, carbon and nitrogen levels were capitalized during evolution such that PII can act as a dissociable regulatory subunit of a range of transporters, transcriptional regulators and enzymes.
Structure
PII proteins exist in trimers in vivo and bind ATP in a cleft between the subunits. There are two flexible loops call the B-loop and T-loop which are involved in regulation of the protein. The T-loop contains a conserved tyrosine which is the site of uridyl attachment.
Following nitrogen starvation, increased intra-cellular concentrations of ammonia cause the de-uridylylation of GlnK. This then binds directly to the ammonia channel AmtB to block ammonia conduction. PII proteins such as SbtB are also implicated in carbon metabolism regulation, these proteins are able to control the activity of Acetyl-CoA carboxylase in plants, algae and Bacteria
