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Structure paper

TitleStructure and organization of heteromeric AMPA-type glutamate receptors.
Journal, issue, pagesScience, Vol. 352, Issue 6285, Page aad3873, Year 2016
Publish dateApr 29, 2016
AuthorsBeatriz Herguedas / Javier García-Nafría / Ondrej Cais / Rafael Fernández-Leiro / James Krieger / Hinze Ho / Ingo H Greger /
PubMed AbstractAMPA-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 ...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.
External linksScience / PubMed:26966189 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.12 - 10.31 Å
Structure data

EMDB-8090, PDB-5ide:
Cryo-EM structure of GluA2/3 AMPA receptor heterotetramer (model I)
Method: EM (single particle) / Resolution: 8.25 Å

EMDB-8091, PDB-5idf:
Cryo-EM structure of GluA2/3 AMPA receptor heterotetramer (model II)
Method: EM (single particle) / Resolution: 10.31 Å

PDB-5fwx:
Crystal structure of the AMPA receptor GluA2/A4 N-terminal domain heterodimer
Method: X-RAY DIFFRACTION / Resolution: 2.5 Å

PDB-5fwy:
Crystal structure of the AMPA receptor GluA2/A3 N-terminal domain heterodimer
Method: X-RAY DIFFRACTION / Resolution: 2.12 Å

Chemicals

ChemComp-SO4:
SULFATE ION / Sulfate

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-HOH:
WATER / Water

ChemComp-GOL:
GLYCEROL / Glycerol

Source
  • rattus norvegicus (Norway rat)
KeywordsTRANSPORT PROTEIN / SIGNALING PROTEIN / AMPA glutamate receptor

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