Functional characterization of a potassium-selective prokaryotic glutamate receptor

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Abstract

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.

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Figure 1: GluR0 is related to eukaryotic GluRs (eGluRs) and to potassium channels.
Figure 2: GluR0 binds L-glutamate, L-glutamine and other amino acids.
Figure 3: GluR0-mediated ion-channel responses.
Figure 4: GluR0 gates a K+-selective Ba2+-sensitive conductance.

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Acknowledgements

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.).

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Correspondence to Eric Gouaux.

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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

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