Ion channels are molecular pores that facilitate the passage of ions across cell membranes and participate in a range of biological processes, from excitatory signal transmission in the mammalian nervous system to the modulation of swimming behaviour in the protozoan Paramecium1. Two particularly important families of ion channels are ionotropic glutamate receptors (GluRs)2 and potassium channels3,4. GluRs are permeable to Na+, K+ and Ca2+, are gated by glutamate, and have previously been found only in eukaryotes2. In contrast, potassium channels are selective for K+, are gated by a range of stimuli, and are found in both prokaryotes and eukaryotes3,4. Here we report the discovery and functional characterization of GluR0 from Synechocystis PCC 6803, which is the first GluR found in a prokaryote. GluR0 binds glutamate, forms potassium-selective channels and is related in amino-acid sequence to both eukaryotic GluRs and potassium channels. On the basis of amino-acid sequence and functional relationships between GluR0 and eukaryotic GluRs, we propose that a prokaryotic GluR was the precursor to eukaryotic GluRs. GluR0 provides evidence for the missing link between potassium channels and GluRs, and we suggest that their ion channels have a similar architecture, that GluRs are tetramers and that the gating mechanisms of GluRs and potassium channels have some essential features in common.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Hille,B. Ionic Channels of Excitable Membranes (Sinauer, Sunderland, Massachusetts, 1992).
Dingledine,R., Borges,K., Bowie,D. & Traynelis,S. F. The glutamate receptor ion channels. Pharmacol. Rev. 51, 7–61 (1999).
Coetzee,W. A. et al. Molecular diversity of K+ channels. Ann. NY Acad. Sci. 868, 233–285 (1999).
Yellen,G. The bacterial K+ channel structure and its implications for neuronal channels. Curr. Opin. Neurobiol. 9, 267–273 (1999).
Altschul,S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997).
Kaneko,T. et al. Sequence analysis of the genome of the unicellular cyanobacterium Synechocystis sp. strain PCC 6803. II. Sequence determination of the entire genome and assignment of potential protein-coding regions. DNA Res. 3, 109–136 (1996).
Lomeli,H. et al. The rat delta-1 and delta-2 subunits extend the excitatory amino acid receptor family. FEBS Lett. 315, 318–322 (1993).
Lam,H. M. et al. Glutamate-receptor genes in plants. Nature 396, 125–126 (1998).
Hollmann,M., O'Shea-Greenfield,A., Rogers,S. W. & Heinemann,S. Cloning by functional expression of a member of the glutamate receptor family. Nature 342, 643–648 (1989).
Keinänen,K. et al. A family of AMPA-selective glutamate receptors. Science 249, 556–560 (1990).
Stern-Bach,Y. et al. Agonist selectivity of glutamate receptors is specified by two domains structurally related to bacterial amino acid-binding proteins. Neuron 13, 1345–1357 (1994).
Kuusinen,A., Arvola,M. & Keinänen,K. Molecular dissection of the agonist binding site of an AMPA receptor. EMBO J. 14, 6327–6332 (1995).
Armstrong,N., Sun,Y., Chen,G.-Q. & Gouaux,E. Structure of a glutamate receptor ligand binding core in complex with kainate. Nature 395, 913–917 (1998).
Lampinen,M., Pentikäinen,O., Johnson,M. S. & Keinänen,K. AMPA receptors and bacterial periplasmic amino acid-binding proteins share the ionic mechanism of ligand recognition. EMBO J. 17, 4704–4711 (1998).
Baro,D. J., Cole,C. L. & Harris-Warrick,R. M. The lobster shaw gene: cloning, sequence analysis and comparison to fly shaw. Gene 170, 267–270 (1996).
Schrempf,H. et al. A prokaryotic potassium ion channel with two predicted transmembrane segments from Streptomyces lividans. EMBO J. 14, 5170–5178 (1995).
Doyle,D. A. et al. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280, 69–77 (1998).
Perozo,E., Cortes,D. M. & Cuello,L. G. Structural rearrangements underlying K+-channel activation gating. Science 285, 73–78 (1999).
Zuo,J. et al. Neurodegeneration in Lurcher mice caused by mutation in δ2 glutamate receptor gene. Nature 388, 769–773 (1997).
Wo,Z. G. & Oswald,R. E. Unraveling the modular design of glutamate-gated ion channels. Trends Neurosci. 18, 161–168 (1995).
Wood,M. W., VanDongen,H. M. & VanDongen,A. M. Structural conservation of ion conduction pathways in K channels and glutamate receptors. Proc. Natl Acad. Sci. USA 92, 4882–4886 (1995).
Chen,G. Q. & Gouaux,E. Overexpression of a glutamate receptor (GluR2) ligand binding domain in Escherichia coli: Application of a novel protein folding screen. Proc. Natl Acad. Sci. USA 94, 13431–13436 (1997).
Heginbotham,L., LeMasurier,M., Kolmakova-Partensky,L. & Miller,C. Single Streptomyces lividans K+ channels. Functional asymmetries and sideness of proton activation. J. Gen. Physiol. 114, 551–559 (1999).
Wada,K. et al. Sequence and expression of a frog brain complementary DNA encoding a kainate-binding protein. Nature 342, 684–689 (1989).
Liman,E. R., Tytgat,J. & Hess,P. Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs. Neuron 9, 861–871 (1992).
Keinänen,K., Köhr,G., Seeburg,P. H., Laukkanen,M.-L. & Oker-Blom,C. High-level expression of functional glutamate receptor channels in insect cells. Bio/Technology 12, 802–806 (1994).
Stern-Bach,Y., Russo,S., Neuman,M. & Rosenmund,C. A point mutation in the glutamate binding site blocks desensitization of AMPA receptors. Neuron 21, 907–918 (1998).
Schreibmayer,W., Lester,H. A. & Dascal,N. Voltage clamping of Xenopus oocytes utilizing agarose-cushion electrodes. Pflügers Arch. 426, 453–458 (1994).
Chen,C. & Okayama,H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol. Cell. Biol. 7, 2745–2752 (1987).
Vyklicky,L., Benveniste,M. & Mayer,M. L. Modulation of N-methyl-D-aspartic acid receptor desensitization by glycine in mouse cultured hippocampal neurones. J. Physiol. (Lond.) 428, 313–331 (1990).
We thank W. J. Vermaas for the Synechocystis PCC 6803 genomic DNA; E. Kandel for encouragement; R. MacKinnon, D. Bryant and B. Ramachandran for comments; the laboratory of D. Hirsh for the use of equipment; and C. Glasser for technical assistance. This work was supported by the Alfred P. Sloan Foundation (E.G.), the NSF Young Investigator Program (E.G.), the Klingenstein Foundation (E.G.), the National Alliance for Research on Schizophrenia and Depression (E.G.) and the NIH (E.G., M.L.M.).
About this article
Cite this article
Chen, G., Cui, C., Mayer, M. et al. Functional characterization of a potassium-selective prokaryotic glutamate receptor. Nature 402, 817–821 (1999) doi:10.1038/45568
International Journal of Molecular Sciences (2019)
Current Biology (2019)
Coupling of a viral K+-channel with a glutamate-binding-domain highlights the modular design of ionotropic glutamate-receptors
Communications Biology (2019)
Polyamine-mediated channel block of ionotropic glutamate receptors and its regulation by auxiliary proteins
Journal of Biological Chemistry (2018)
Current Opinion in Physiology (2018)