Pii nitrogen regulatory proteins

Nitrogen regulatory protein P-II
GlnB protein from E.coli. PDB 2pii[1] The GlnB protein in E. coli is 68% identical to GlnK.
Identifiers
Symbol	P-II
Pfam	PF00543
Pfam clan	CL0089
InterPro	IPR002187
SMART	SM00938
PROSITE	PDOC00439
SCOP2	1pil / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The P_II 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.^[2] P_II form barrel-like homotrimers with a flexible loop, namely T-loop, emerging from each subunit.^[2] P_II 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 P_II in three conserved binding sites located in the lateral cavity between each P_II subunit. ATP and ADP bind competitively to the nucleotide binding whereas the 2-oxoglutarate only interacts with P_II in the presence of MgATP.^[3]

In Proteobacteria, P_II proteins are also subject to a cycle of reversible posttranslational modification (Huergo et al., 2013). 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 P_II T-loop. Conversely, under a high nitrogen regime, accumulation of intracellular glutamine triggers the uridylyl-removing activity of GlnD and P_II accumulates in its non-modified form (Huergo et al., 2013).

The ability of P_II to sense important metabolites and integrate signals deriving from energy status (ATP and ADP ratio), carbon (2-oxogluratate) and nitrogen (glutamine and 2-oxoglutarate) levels were capitalized during evolution such that P_II can act as a dissociable regulatory subunit of a range of transporters, transcriptional regulators and enzymes.^[4]

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.^[5][6] 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 ^[7]