Glutamate receptors at atomic resolution

  title={Glutamate receptors at atomic resolution},
  author={Mark L Mayer},
  • M. Mayer
  • Published 22 March 2006
  • Biology
  • Nature
At synapses throughout the brain and spinal cord, the amino-acid glutamate is the major excitatory neurotransmitter. During evolution, a family of glutamate-receptor ion channels seems to have been assembled from a kit consisting of discrete ligand-binding, ion-channel, modulatory and cytoplasmic domains. Crystallographic studies that exploit this unique architecture have greatly aided structural analysis of the ligand-binding core, but the results also pose a formidable challenge, namely that… 
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Emerging models of glutamate receptor ion channel structure and function.
Glutamate receptor desensitization is mediated by changes in quaternary structure of the ligand binding domain
Using single-particle cryoelectron tomography to determine the structures of full-length GluK2 kainate receptors trapped in antagonist-bound resting and agonist-bound desensitized states, a structural model for differences in quaternary conformation is derived.
Structural mechanism of glutamate receptor activation and desensitization
It is shown that transition to the active state involves a ‘corkscrew’ motion of the receptor assembly, driven by closure of the ligand-binding domain, and a molecular explanation for key steps in receptor gating is provided.
Functional insights from glutamate receptor ion channel structures.
X-ray crystal structures for the soluble amino-terminal and ligand-binding domains of glutamate receptor ion channels, combined with a 3.6-Å-resolution structure of the full-length AMPA receptor
Structural basis of kainate subtype glutamate receptor desensitization
It is shown that desensitization is characterized by the establishment of a ring-like structure in the ligand-binding domain layer of the receptor, mediated by staggered helix contacts between adjacent subunits, which leads to a pseudo-four-fold symmetric arrangement of the lig and-binding domains, illustrating subtle changes in symmetry that are important for the gating mechanism.
Crystal structures of the glutamate receptor ion channel GluK3 and GluK5 amino-terminal domains.


Structure and gating of the glutamate receptor ion channel
The tetrameric structure of a glutamate receptor channel.
Successful application of a counting method in an HEK cell line provides evidence that ionotropic glutamate receptors share a tetrameric structure with the voltage-gated potassium channels.
Roles and rules of kainate receptors in synaptic transmission
  • J. Lerma
  • Biology
    Nature Reviews Neuroscience
  • 2003
Pre- and postsynaptic kainate receptors can regulate transmission at many synapses in a specific manner, and seem to be involved in short- and long-term plastic phenomena, highlighting their significance for synaptic signalling.
Subunit arrangement and function in NMDA receptors
Excitatory neurotransmission mediated by NMDA (N-methyl-d-aspartate) receptors is fundamental to the physiology of the mammalian central nervous system. These receptors are heteromeric ion channels
Activation of NR1/NR2B NMDA receptors
A new working model of receptor activation is proposed that can account for macroscopic as well as microscopic NMDA receptor properties and suggests that NR1 and NR2B subunits, respectively, undergo a fast and slow agonist-dependent conformational change that precedes opening of the pore.
Binding Site Flexibility: Molecular Simulation of Partial and Full Agonists within a Glutamate Receptor
Examination of water molecules surrounding the ligands reveals that mobility in distinct subsites can be a discriminator between full and partial agonism and will be an important consideration in the design of drugs against these receptors.
A common architecture for K+ channels and ionotropic glutamate receptors?