RGD Reference Report - Structure and organization of heteromeric AMPA-type glutamate receptors. - Rat Genome Database

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Structure and organization of heteromeric AMPA-type glutamate receptors.

Authors: Herguedas, Beatriz  García-Nafría, Javier  Cais, Ondrej  Fernández-Leiro, Rafael  Krieger, James  Ho, Hinze  Greger, Ingo H 
Citation: Herguedas B, etal., Science. 2016 Apr 29;352(6285):aad3873. doi: 10.1126/science.aad3873. Epub 2016 Mar 10.
RGD ID: 13432296
Pubmed: PMID:26966189   (View Abstract at PubMed)
PMCID: PMC4852135   (View Article at PubMed Central)
DOI: DOI:10.1126/science.aad3873   (Journal Full-text)

AMPA-type glutamate receptors (AMPARs), which are central mediators of rapid neurotransmission and synaptic plasticity, predominantly exist as heteromers of the subunits GluA1 to GluA4. Here we report the first AMPAR heteromer structures, which deviate substantially from existing GluA2 homomer structures. Crystal structures of the GluA2/3 and GluA2/4 N-terminal domains reveal a novel compact conformation with an alternating arrangement of the four subunits around a central axis. This organization is confirmed by cysteine cross-linking in full-length receptors, and it permitted us to determine the structure of an intact GluA2/3 receptor by cryogenic electron microscopy. Two models in the ligand-free state, at resolutions of 8.25 and 10.3 angstroms, exhibit substantial vertical compression and close associations between domain layers, reminiscent of N-methyl-D-aspartate receptors. Model 1 resembles a resting state and model 2 a desensitized state, thus providing snapshots of gating transitions in the nominal absence of ligand. Our data reveal organizational features of heteromeric AMPARs and provide a framework to decipher AMPAR architecture and signaling.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Gria2  (glutamate ionotropic receptor AMPA type subunit 2)
Gria3  (glutamate ionotropic receptor AMPA type subunit 3)
Gria4  (glutamate ionotropic receptor AMPA type subunit 4)


Additional Information