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Structure paper

TitleArchitecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM.
Journal, issue, pagesScience, Vol. 364, Issue 6438, Page 355-362, Year 2019
Publish dateApr 26, 2019
AuthorsYan Zhao / Shanshuang Chen / Adam C Swensen / Wei-Jun Qian / Eric Gouaux /
PubMed AbstractGlutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric ...Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric assemblies composed of four subunits, GluA1-GluA4. Despite decades of study, the subunit composition, subunit arrangement, and molecular structure of native AMPA receptors remain unknown. Here we elucidate the structures of 10 distinct native AMPA receptor complexes by single-particle cryo-electron microscopy (cryo-EM). We find that receptor subunits are arranged nonstochastically, with the GluA2 subunit preferentially occupying the B and D positions of the tetramer and with triheteromeric assemblies comprising a major population of native AMPA receptors. Cryo-EM maps define the structure for S2-M4 linkers between the ligand-binding and transmembrane domains, suggesting how neurotransmitter binding is coupled to ion channel gating.
External linksScience / PubMed:30975770 / PubMed Central
MethodsEM (single particle)
Resolution4.5 - 32.0 Å
Structure data

EMDB-0426:
Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM
Method: EM (single particle) / Resolution: 12.8 Å

EMDB-0427:
Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM
Method: EM (single particle) / Resolution: 22.0 Å

EMDB-0428:
Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM
Method: EM (single particle) / Resolution: 32.0 Å

EMDB-0429:
Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM
Method: EM (single particle) / Resolution: 12.8 Å

EMDB-0430:
Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM
Method: EM (single particle) / Resolution: 8.7 Å

EMDB-0431:
Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM
Method: EM (single particle) / Resolution: 23.0 Å

EMDB-0432:
Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM
Method: EM (single particle) / Resolution: 21.0 Å

EMDB-20085:
structure of a complex
Method: EM (single particle) / Resolution: 4.5 Å

9387

6njl

EMDB-9387, PDB-6njl:
Architecture and subunit arrangement of native AMPA receptors
Method: EM (single particle) / Resolution: 6.7 Å

9388

6njm

EMDB-9388, PDB-6njm:
Architecture and subunit arrangement of native AMPA receptors
Method: EM (single particle) / Resolution: 6.5 Å

9389

6njn

EMDB-9389, PDB-6njn:
Architecture and subunit arrangement of native AMPA receptors
Method: EM (single particle) / Resolution: 6.5 Å

Chemicals

ChemComp-ZK1:
{[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid / antagonist, medication*YM / Fanapanel

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

Source
  • rattus norvegicus (Norway rat)
  • Rat (rat)
  • mus musculus (house mouse)
KeywordsMEMBRANE PROTEIN/IMMUNE SYSTEM / AMPA receptor / ligand gated ion channel / neurotransmitter / synapse / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex

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