5up2

Triheteromeric NMDA receptor GluN1/GluN2A/GluN2B in complex with glycine, glutamate, Ro 25-6981, MK-801 and a GluN2B-specific Fab, at pH 6.5

Loading... Status: waiting for Mol* initialization Structural highlights 5up2 is a 6 chain structure with sequence from African clawed frog and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAG NonStd Res: UNK Related: 5uow Gene: LOC100127346 (African clawed frog), NR2B (African clawed frog) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed N-methyl-D-aspartate receptors (NMDARs) are heterotetrameric ion channels assembled as diheteromeric or triheteromeric complexes. Here, we report structures of the triheteromeric GluN1/GluN2A/GluN2B receptor in the absence or presence of the GluN2B-specific allosteric modulator Ro 25-6981 (Ro), determined by cryogenic electron microscopy (cryo-EM). In the absence of Ro, the GluN2A and GluN2B amino terminal domains (ATD) adopt "closed" and "open" clefts, respectively. Upon binding Ro, the GluN2B ATD clamshell transitions from an open to a closed conformation. Consistent with a predominance of the GluN2A subunit in ion channel gating, the GluN2A subunit interacts more extensively with GluN1 subunits throughout the receptor, in comparison with the GluN2B subunit. Differences in the conformation of the pseudo 2-fold related GluN1 subunits further reflect receptor asymmetry. The triheteromeric NMDAR structures provide the first view of the most common NMDA receptor assembly and show how incorporation of two different GluN2 subunits modifies receptor symmetry and subunit interactions, allowing each subunit to uniquely influence receptor structure and function, thus increasing receptor complexity. Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation.,Lu W, Du J, Goehring A, Gouaux E Science. 2017 Feb 23. pii: eaal3729. doi: 10.1126/science.aal3729. PMID:28232581 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutamate receptor 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA