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

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, GluA1-4. 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.

Authors:
 [1];  [1];  [2]; ORCiD logo [2];  [1]
  1. Oregon Health & Science University
  2. BATTELLE (PACIFIC NW LAB)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1543312
Report Number(s):
PNNL-SA-141540
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Science
Additional Journal Information:
Journal Volume: 364; Journal Issue: 6438
Country of Publication:
United States
Language:
English

Citation Formats

Zhao, Yan, Shanshuang, Chen, Swensen, Adam C., Qian, Weijun, and Gouaux, Eric. Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM. United States: N. p., 2019. Web. doi:10.1126/science.aaw8250.
Zhao, Yan, Shanshuang, Chen, Swensen, Adam C., Qian, Weijun, & Gouaux, Eric. Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM. United States. doi:10.1126/science.aaw8250.
Zhao, Yan, Shanshuang, Chen, Swensen, Adam C., Qian, Weijun, and Gouaux, Eric. Fri . "Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM". United States. doi:10.1126/science.aaw8250.
@article{osti_1543312,
title = {Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM},
author = {Zhao, Yan and Shanshuang, Chen and Swensen, Adam C. and Qian, Weijun and Gouaux, Eric},
abstractNote = {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.},
doi = {10.1126/science.aaw8250},
journal = {Science},
number = 6438,
volume = 364,
place = {United States},
year = {2019},
month = {4}
}