Human NMDA receptor family channel gating by GluN1 and its partner subunits

How the heterotetrameric receptors built on the GluN1 subunit are opened. Every receptor of this family contains two GluN1 subunits, which bind the co-agonist glycine or D-serine, and two partner subunits. With GluN2 partners (GluN2A to GluN2D) the partner binds glutamate, and the channel opens only when both ligands are bound; the open pore conducts sodium, potassium and calcium and is blocked by magnesium at resting potential, so current also requires depolarisation. With GluN3 partners (GluN3A or GluN3B) both subunit types bind glycine and glutamate is not needed: glycine at GluN3 opens the channel, whereas glycine at GluN1 limits the current. These channels have low calcium permeability and no magnesium block. The module covers ligand sensing by each subunit and conduction by the assembled tetramer. Receptor assembly and trafficking, synaptic anchoring by PSD-95 family scaffolds, allosteric modulation, and signalling downstream of calcium entry are outside it.

Tri-heteromeric receptors (two different GluN2 subunits, or one GluN2 and one GluN3) exist and are not modelled as separate variants. The choice of partner in part 2 fixes the conduction variant in part 3: a GluN2 partner gives NMDA glutamate receptor activity, a GluN3 partner gives glycine-gated cation channel activity; the schema does not link the two variant sets, so this is stated here. Magnesium block and its relief by depolarisation are described in prose only. Potassium efflux is known for these channels but is not listed as a transported ion, to match the evidence checked. Only GRIN1 has a gene review in this repository; the six partner subunits do not, so status is DRAFT. PANTHER family and PAINT node descriptors are omitted because subfamily membership of each subunit was not verified. The seven GO-CAM models pinned here were reviewed in gocams/<model>/<model>-review.yaml. They type each subunit with the whole-receptor activity and add a third, complex-enabled activity; this module instead gives each subunit its ligand-binding step and puts conduction on the complex. The sign of GluN1 glycine binding differs by receptor class and is modelled as two connections; the GluN1 glycine-site GO-CAM activities in the two GluN3 models draw it as positive, which the GO-CAM reviews query. Location: the GluN3A glycine-site annoton is placed at the postsynaptic membrane, following the GO-CAM model; no location is asserted for GluN3B or for the GluN1/GluN3 channel, because rat GluN3B shows a presynaptic labelling pattern (PMID:23159309) and the GO-CAM model for it mixes pre- and postsynaptic membranes. Module deep research (OpenScientist) was run after the module was drafted, with the module as its outline.