Structural insights into gating mechanism and allosteric regulation of NMDA receptors.

Journal: Current opinion in neurobiology
PMID: 37950957

Abstract

N-methyl-d-aspartate receptors (NMDARs) belong to the ionotropic glutamate receptors (iGluRs) superfamily and act as coincidence detectors that are crucial to neuronal development and synaptic plasticity. They typically assemble as heterotetramers of two obligatory GluN1 subunits and two alternative GluN2 (from 2A to 2D) and/or GluN3 (3A and 3B) subunits. These alternative subunits mainly determine the diverse biophysical and pharmacological properties of different NMDAR subtypes. Over the past decade, the unprecedented advances in structure elucidation of these tetrameric NMDARs have provided atomic insights into channel gating, allosteric modulation and the action of therapeutic drugs. A wealth of structural and functional information would accelerate the artificial intelligence-based drug design to exploit more NMDAR subtype-specific molecules for the treatment of neurological and psychiatric disorders.

Authors

  • Enjiang Wu
    Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: https://twitter.com/DuDaDa_Flower.
  • Jilin Zhang
  • Jiwei Zhang
    School of Mathematics and Statistics, Wuhan University, Wuhan, 430072, China.
  • Shujia Zhu
    Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: shujiazhu@ion.ac.cn.

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