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Glutamate receptors at atomic resolution

Nature volume 440, pages 456–462 (2006)Cite this article

Abstract

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 of resolving the allosteric mechanisms by which individual domains communicate and function in an intact receptor.

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Figure 1: Modular organization of a glutamate receptor.
Figure 2: Conserved structural elements in the agonist-binding site of iGluRs.
Figure 3: Solvent-accessible surfaces of the ligand-binding cavity in iGluR agonist crystal structures.
Figure 4: Activation of iGluR gating, resulting from agonist-induced expansion of the ligand-binding core dimer.
Figure 5: The pore region of the KcsA potassium channel used as a template to map the results of site-directed mutagenesis on iGluR channel block by polyamines.

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Acknowledgements

Work in the author's laboratory is supported by the intramural research programme of NICHD, NIH, DHHS. Synchotron diffraction data were collected at Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline at the Advanced Photon Source, Argonne National Laboratory. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences.

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Mayer, M. Glutamate receptors at atomic resolution. Nature 440, 456–462 (2006). https://doi.org/10.1038/nature04709

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