Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Neuron
2008 Jan 10;571:80-93. doi: 10.1016/j.neuron.2007.11.021.
Show Gene links
Show Anatomy links
Structural rearrangements of NR1/NR2A NMDA receptors during allosteric inhibition.
Gielen M, Le Goff A, Stroebel D, Johnson JW, Neyton J, Paoletti P.
???displayArticle.abstract???
Ionotropic glutamate receptor (iGluR) subunits contain a large N-terminal domain (NTD) that precedes the agonist-binding domain (ABD) and participates in subunit oligomerization. In NMDA receptors (NMDARs), the NTDs of NR2A and NR2B subunits also form binding sites for the endogenous inhibitor Zn(2+) ion. Although these allosteric sites have been characterized in detail, the molecular mechanisms by which the NTDs communicate with the rest of the receptor to promote its inhibition remain unknown. Here, we identify the ABD dimer interface as a major structural determinant that permits coupling between the NTDs and the channel gate. The strength of this interface also controls proton inhibition, another form of allosteric modulation of NMDARs. Conformational rearrangements at the ABD dimer interface thus appear to be a key mechanism conserved in all iGluR subfamilies, but have evolved to fulfill different functions: fast desensitization at AMPA and kainate receptors, allosteric inhibition at NMDARs.
Armstrong,
Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor.
2006, Pubmed,
Xenbase
Armstrong,
Measurement of conformational changes accompanying desensitization in an ionotropic glutamate receptor.
2006,
Pubmed
,
Xenbase Ayalon,
Two regions in the N-terminal domain of ionotropic glutamate receptor 3 form the subunit oligomerization interfaces that control subtype-specific receptor assembly.
2005,
Pubmed Choi,
Identification and mechanism of action of two histidine residues underlying high-affinity Zn2+ inhibition of the NMDA receptor.
1999,
Pubmed
,
Xenbase Dingledine,
The glutamate receptor ion channels.
1999,
Pubmed Erreger,
Allosteric interaction between zinc and glutamate binding domains on NR2A causes desensitization of NMDA receptors.
2005,
Pubmed Fayyazuddin,
Four residues of the extracellular N-terminal domain of the NR2A subunit control high-affinity Zn2+ binding to NMDA receptors.
2000,
Pubmed
,
Xenbase Furukawa,
Subunit arrangement and function in NMDA receptors.
2005,
Pubmed Hatton,
Modulation of triheteromeric NMDA receptors by N-terminal domain ligands.
2005,
Pubmed
,
Xenbase Horning,
Regulation of AMPA receptor gating by ligand binding core dimers.
2004,
Pubmed Ihle,
Modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor desensitization by extracellular protons.
2000,
Pubmed Jin,
Structural basis for partial agonist action at ionotropic glutamate receptors.
2003,
Pubmed
,
Xenbase Jingami,
Structure of the metabotropic glutamate receptor.
2003,
Pubmed Kew,
A novel mechanism of activity-dependent NMDA receptor antagonism describes the effect of ifenprodil in rat cultured cortical neurones.
1996,
Pubmed Kuusinen,
Oligomerization and ligand-binding properties of the ectodomain of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit GluRD.
1999,
Pubmed Lei,
Positive allosteric modulators of AMPA receptors reduce proton-induced receptor desensitization in rat hippocampal neurons.
2001,
Pubmed Low,
Molecular determinants of coordinated proton and zinc inhibition of N-methyl-D-aspartate NR1/NR2A receptors.
2000,
Pubmed
,
Xenbase Low,
Molecular determinants of proton-sensitive N-methyl-D-aspartate receptor gating.
2003,
Pubmed
,
Xenbase Madry,
The N-terminal domains of both NR1 and NR2 subunits determine allosteric Zn2+ inhibition and glycine affinity of N-methyl-D-aspartate receptors.
2007,
Pubmed
,
Xenbase Mayer,
Glutamate receptors at atomic resolution.
2006,
Pubmed Meddows,
Identification of molecular determinants that are important in the assembly of N-methyl-D-aspartate receptors.
2001,
Pubmed
,
Xenbase O'Neil,
A thermodynamic scale for the helix-forming tendencies of the commonly occurring amino acids.
1990,
Pubmed Paoletti,
High-affinity zinc inhibition of NMDA NR1-NR2A receptors.
1997,
Pubmed
,
Xenbase Paoletti,
Molecular organization of a zinc binding n-terminal modulatory domain in a NMDA receptor subunit.
2000,
Pubmed
,
Xenbase Paoletti,
Glycine-independent and subunit-specific potentiation of NMDA responses by extracellular Mg2+.
1995,
Pubmed
,
Xenbase Paoletti,
NMDA receptor subunits: function and pharmacology.
2007,
Pubmed Perin-Dureau,
Mapping the binding site of the neuroprotectant ifenprodil on NMDA receptors.
2002,
Pubmed
,
Xenbase Plested,
Structure and mechanism of kainate receptor modulation by anions.
2007,
Pubmed Priel,
Block of kainate receptor desensitization uncovers a key trafficking checkpoint.
2006,
Pubmed
,
Xenbase Rachline,
The micromolar zinc-binding domain on the NMDA receptor subunit NR2B.
2005,
Pubmed
,
Xenbase Sine,
Recent advances in Cys-loop receptor structure and function.
2006,
Pubmed Smart,
Zn2+ ions: modulators of excitatory and inhibitory synaptic activity.
2004,
Pubmed Sun,
Mechanism of glutamate receptor desensitization.
2002,
Pubmed Traynelis,
Pharmacological properties and H+ sensitivity of excitatory amino acid receptor channels in rat cerebellar granule neurones.
1991,
Pubmed Traynelis,
Proton release as a modulator of presynaptic function.
2001,
Pubmed Vogt,
The actions of synaptically released zinc at hippocampal mossy fiber synapses.
2000,
Pubmed Westbrook,
Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons.
,
Pubmed Weston,
Conformational restriction blocks glutamate receptor desensitization.
2006,
Pubmed Zheng,
Allosteric interaction between the amino terminal domain and the ligand binding domain of NR2A.
2001,
Pubmed
