Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM

Zhao, Yan; Shanshuang, Chen; Swensen, Adam C.; Qian, Weijun; Gouaux, Eric

doi:10.1126/science.aaw8250

Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM

Journal Article · Fri Apr 26 04:00:00 EDT 2019 · Science

DOI:https://doi.org/10.1126/science.aaw8250· OSTI ID:1543312

Zhao, Yan ^[1]; Shanshuang, Chen ^[1]; Swensen, Adam C. ^[2]; ^[2]; Gouaux, Eric ^[1]

Oregon Health & Science University
BATTELLE (PACIFIC NW LAB)

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, GluA1-4. Despite decades of study, the subunit composition, subunit arrangement, and molecular structure of native AMPA receptors remains unknown. Here we elucidate the structure of 10 distinct native AMPA receptor complexes by single particle cryo-EM. We find that receptor subunits are arranged non-stochastically, with the GluA2 subunit preferentially occupying the B/D positions of the tetramer and with triheteromeric assemblies comprising a major population of native AMPA receptors. Density maps define the structure for previously unseen linking peptides between the ligand binding and transmembrane domains, showing how neurotransmitter binding is coupled to ion channel gating.

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1543312

Report Number(s):: PNNL-SA-141540

Journal Information:: Science, Journal Name: Science Journal Issue: 6438 Vol. 364

Country of Publication:: United States

Language:: English

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