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Architecture and Subunit Arrangement of Native AMPA Receptors Elucidated by cryo-EM

Yan Zhao, Shanshuang Chen, Adam C Swensen, Wei-Jun Qian, Eric Gouaux

Science. 2019 Apr 26;364(6438):355-362.

PMID: 30975770

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP74341632 (±)-AMPA (±)-AMPA 74341-63-2 Price
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