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Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels

Nature Structural & Molecular Biology volume 23, pages 494–502 (2016)Cite this article

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Numerous recent crystal and cryo-EM structures have greatly advanced understanding of the functional mechanisms of neurotransmitter-gated ion channels. This Review discusses the structural basis of activation and desensitization mechanisms in glutamate and cysteine-loop receptors.

Abstract

Ion channels gated by neurotransmitters are present across metazoans, in which they are essential for brain function, sensation and locomotion; closely related homologs are also found in bacteria. Structures of eukaryotic pentameric cysteine-loop (Cys-loop) receptors and tetrameric ionotropic glutamate receptors in multiple functional states have recently become available. Here, I describe how these studies relate to established ideas regarding receptor activation and how they have enabled decades' worth of functional work to be pieced together, thus allowing previously puzzling aspects of receptor activity to be understood.

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Figure 1: Architecture and neurotransmitter binding in GluRs.
Figure 2: Architecture and ligand binding in CLRs.
Figure 3: Gating and desensitization of CLRs.
Figure 4: Gating and desensitization in GluRs.
Figure 5: Interfaces in CLRs and GluRs.

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Acknowledgements

I thank J. Baranovic, M. Poulsen, C. Eibl, C. Czajkowski and C. Grosman for comments on the manuscript. Figures were prepared with PyMOL (http://www.pymol.org/) and the UCSF Chimera package119. Chimera was developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311).

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  1. Leibniz-Institut für Molekulare Pharmakologie (FMP), Berlin, Germany

    Andrew J R Plested

  2. NeuroCure, Charité-Universitätsmedizin Berlin, Berlin, Germany

    Andrew J R Plested

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Plested, A. Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels. Nat Struct Mol Biol 23, 494–502 (2016). https://doi.org/10.1038/nsmb.3214

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