Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation
Open accessAbstract
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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Allosteric ligands do not have to compete with high-affinity substrates, making it simpler to develop allosteric modulators.
“Firstly, allosteric ligands do not have to compete with high-affinity substrates, making it simpler to develop allosteric modulators.”
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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
- PMC
- PMC5568803
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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