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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)355-362
Number of pages8
JournalScience
Volume364
Issue number6438
DOIs
StatePublished - Apr 26 2019

Fingerprint

Cryoelectron Microscopy
AMPA Receptors
Ion Channel Gating
Molecular Structure
Synapses
Neurotransmitter Agents
Glutamic Acid
Signal Transduction
Ligands
Brain
Population

ASJC Scopus subject areas

  • General

Cite this

Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM. / Zhao, Yan; Chen, Shanshuang; Swensen, Adam C.; Qian, Wei Jun; Gouaux, Eric.

In: Science, Vol. 364, No. 6438, 26.04.2019, p. 355-362.

Research output: Contribution to journalArticle

Zhao, Yan ; Chen, Shanshuang ; Swensen, Adam C. ; Qian, Wei Jun ; Gouaux, Eric. / Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM. In: Science. 2019 ; Vol. 364, No. 6438. pp. 355-362.
@article{8d02db851ee34d1bbe9b6169c5168c49,
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–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.",
author = "Yan Zhao and Shanshuang Chen and Swensen, {Adam C.} and Qian, {Wei Jun} and Eric Gouaux",
year = "2019",
month = "4",
day = "26",
doi = "10.1126/science.aaw8250",
language = "English (US)",
volume = "364",
pages = "355--362",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6438",

}

TY - JOUR

T1 - Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM

AU - Zhao, Yan

AU - Chen, Shanshuang

AU - Swensen, Adam C.

AU - Qian, Wei Jun

AU - Gouaux, Eric

PY - 2019/4/26

Y1 - 2019/4/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85065345603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065345603&partnerID=8YFLogxK

U2 - 10.1126/science.aaw8250

DO - 10.1126/science.aaw8250

M3 - Article

VL - 364

SP - 355

EP - 362

JO - Science

JF - Science

SN - 0036-8075

IS - 6438

ER -