title: Activation-induced structural change in the GluN1/GluN3A excitatory glycine receptor.
abstract: Unlike GluN2-containing N-methyl-d-aspartate (NMDA) receptors, which require both glycine and glutamate for activation, receptors composed of GluN1 and GluN3 subunits are activated by glycine alone. Here, we used atomic force microscopy (AFM) imaging to examine the response to activation of the GluN1/GluN3A excitatory glycine receptor. GluN1 and GluN3A subunits were shown to interact intimately within transfected tsA 201 cells. Isolated GluN1/GluN3A receptors integrated into lipid bilayers responded to addition of either glycine or d-serine, but not glutamate, with a ∼1 nm reduction in height of the extracellular domain. The height reduction in response to glycine was abolished by the glycine antagonist 5,7-dichlorokynurenic acid. Our results represent the first demonstration of the effect of activation on the conformation of this receptor.
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
authors.forename: Dilshan
authors.initials: D
authors.lastname: Balasuriya
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
authors.forename: Hirohide
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
authors.forename: Shyam
authors.initials: S
authors.lastname: Srivats
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom. Electronic address: jme1000@cam.ac.uk.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Edwardson
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D017470:Receptors, Glutamate
keywords: Atomic force microscopy; Excitatory glycine receptor; Ionotropic glutamate receptor; NMDA receptor; Receptor activation