Cited by 176Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingNicotinic Acetylcholine Receptors Study

Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation

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Lü, Wei, Du, Juan, Goehring, April, Gouaux, Eric·2017·Science

Abstract

Added complexity in an asymmetric receptor: N -methyl- d -aspartate receptors (NMDARs) are heterotetrameric ion channels that initiate chemical and electrical signals in postsynaptic cells. They play key roles in brain development and function and are the targets of drugs for treating neurological disorders such as schizophrenia, depression, and epilepsy. For the channel to open, it must bind glutamate and glycine and release a blocking magnesium ion. Most NMDARs have three different subunits that bind glycine and glutamine, but structural studies have focused on tetramers of only two subunits. Lü et al. determined the structure of triheteromeric NMDAR. The structural studies show how having three different subunits modifies receptor symmetry and subunit interactions and increases the complexity of receptor regulation. Science , this issue p. eaal3729

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Authors
Lü, W., Du, J., Goehring, A., & Gouaux, E.
Affiliations
  • Oregon Health & Science University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Lü, Wei
  • Du, Juan
  • Gouaux, Eric
Venue
Science
Published
2017-03-24
Volume
355
Issue
6331
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2590999072
Cited by
176
References
67
Citations by year
2026: 9 · 2025: 15 · 2024: 17 · 2023: 20 · 2022: 15 · 2021: 21 · 2020: 20 · 2019: 19 · 2018: 26 · 2017: 13
FWCI
10.70
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (award294565, R01NS038631)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
NMDA receptor, allosteric modulation, Ro 25-6981, N-terminal domain, channel gating, subunit interactions, ion channel structure
MeSH terms
Protein Domains, Allosteric Regulation, Animals, Antibodies, Monoclonal, Models, Molecular, Neuronal Plasticity, Xenopus laevis, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Cryoelectron Microscopy, Xenopus Proteins, Protein Multimerization

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