A modern ionotropic glutamate receptor with a K+ selectivity signature sequence (original) (raw)
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PLoS ONE, 2010
Voltage-gated and ligand-gated ion channels are used in eukaryotic organisms for the purpose of electrochemical signaling. There are prokaryotic homologues to major eukaryotic channels of these sorts, including voltage-gated sodium, potassium, and calcium channels, Ach-receptor and glutamate-receptor channels. The prokaryotic homologues have been less well characterized functionally than their eukaryotic counterparts. In this study we identify likely prokaryotic functional counterparts of eukaryotic glutamate receptor channels by comprehensive analysis of the prokaryotic sequences in the context of known functional domains present in the eukaryotic members of this family. In particular, we searched the nonredundant protein database for all proteins containing the following motif: the two sections of the extracellular glutamate binding domain flanking two transmembrane helices. We discovered 100 prokaryotic sequences containing this motif, with a wide variety of functional annotations. Two groups within this family have the same topology as eukaryotic glutamate receptor channels. Group 1 has a potassium-like selectivity filter. Group 2 is most closely related to eukaryotic glutamate receptor channels. We present analysis of the functional domain architecture for the group of 100, a putative phylogenetic tree, comparison of the protein phylogeny with the corresponding species phylogeny, consideration of the distribution of these proteins among classes of prokaryotes, and orthologous relationships between prokaryotic and human glutamate receptor channels. We introduce a construct called the Evolutionary Domain Network, which represents a putative pathway of domain rearrangements underlying the domain composition of present channels. We believe that scientists interested in ion channels in general, and ligand-gated ion channels in particular, will be interested in this work. The work should also be of interest to bioinformatics researchers who are interested in the use of functional domain-based analysis in evolutionary and functional discovery.
Molecular and Cellular Neuroscience, 2006
The canonical potassium channel selectivity filter motif TVGYG was transplanted into ionotropic glutamate receptors (iGluRs) of the AMPA and NMDA subtype to test whether it renders the iGluRs K + selective. The TVGYG motif modulated several ion pore properties of AMPA receptor as well as NMDA receptor mutants, e.g., the intraand extracellular polyamine block, current/voltage relationships, open channel block by MK801 and Mg 2+ , and permeability for divalent cations. However, introduction of the selectivity filter failed to increase the K + selectivity of homomeric AMPA and heteromeric NMDA receptor complexes, which may be due to absence of selectivity filterstabilizing interaction sites in the iGluR pore domain.
Ionotropic glutamate receptors in GtoPdb v.2021.3
IUPHAR/BPS Guide to Pharmacology CITE, 2021
The ionotropic glutamate receptors comprise members of the NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) and kainate receptor classes, named originally according to their preferred, synthetic, agonist [35, 92, 155]. Receptor heterogeneity within each class arises from the homo-oligomeric, or hetero-oligomeric, assembly of distinct subunits into cation-selective tetramers. Each subunit of the tetrameric complex comprises an extracellular amino terminal domain (ATD), an extracellular ligand binding domain (LBD), 3 TM domains (M1, M3 and M4), a channel lining re-entrant 'p-loop' (M2) located between M1 and M3 and an intracellular carboxy- terminal domain (CTD) [99, 68, 107, 155, 82]. The X-ray structure of a homomeric ionotropic glutamate receptor (GluA2- see below) has recently been solved at 3.6Å resolution [143] and although providing the most complete structural information current available may not representative of the subunit a...
Ionotropic glutamate receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
IUPHAR/BPS Guide to Pharmacology CITE, 2019
The ionotropic glutamate receptors comprise members of the NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) and kainate receptor classes, named originally according to their preferred, synthetic, agonist [34, 87, 147]. Receptor heterogeneity within each class arises from the homo-oligomeric, or hetero-oligomeric, assembly of distinct subunits into cation-selective tetramers. Each subunit of the tetrameric complex comprises an extracellular amino terminal domain (ATD), an extracellular ligand binding domain (LBD), three transmembrane domains composed of three membrane spans (M1, M3 and M4), a channel lining re-entrant ‘p-loop’ (M2) located between M1 and M3 and an intracellular carboxy- terminal domain (CTD) [94, 66, 102, 147, 77]. The X-ray structure of a homomeric ionotropic glutamate receptor (GluA2 – see below) has recently been solved at 3.6Å resolution [135] and although providing the most complete structural information current availabl...
The glutamate receptor ion channels
Pharmacological reviews, 1999
The ionotropic glutamate receptors are ligand-gated ion channels that mediate the vast majority of excitatory neurotransmission in the brain. The cloning of cDNAs encoding glutamate receptor subunits, which occurred mainly between 1989 and 1992 ([Hollmann and Heinemann, 1994][1]), stimulated this
Molecular and Cellular Neuroscience, 2006
The pore domains of ionotropic glutamate receptors (iGluRs) and potassium channels (K + channels) show several structural similarities. To test for functional compatibility, we transferred pore regions from prokaryotic, invertebrate, and vertebrate K + channels into pharmacologically representative iGluRs and vice versa. Although the chimeric proteins were expressed on the cell surface, only one of 45 pore chimeras showed ion channel function: The kainate receptor subunit GluR6, carrying the pore loop plus adjacent transmembrane domains of the prokaryotic, glutamategated, K + -selective GluR0, adopted several electrophysiological properties of the donor pore upon pore transplantation. This suggests that, despite structural similarities between iGluR and K + channel pores, there is a lack of functional compatibility so that K + channel pores cannot be gated by the iGluR gating machinery, and vice versa. However, K + -selective pores can be gated in an iGluR sequence environment, given a similar signal transduction mechanism as appears to be present in GluR0.
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Pharmacological Reviews, 2010
The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
Scientific reports, 2015
Glutamate is an indispensable neurotransmitter, triggering postsynaptic signals upon recognition by postsynaptic receptors. We questioned the phylogenetic position and the molecular details of when and where glutamate recognition arose in the glutamate-gated chloride channels. Experiments revealed that glutamate recognition requires an arginine residue in the base of the binding site, which originated at least three distinct times according to phylogenetic analysis. Most remarkably, the arginine emerged on the principal face of the binding site in the Lophotrochozoan lineage, but 65 amino acids upstream, on the complementary face, in the Ecdysozoan lineage. This combined experimental and computational approach throws new light on the evolution of synaptic signalling.
Structural characteristics of ionotropic glutamate receptors as identified by channel blockade
2002
Glutamate is far from the only (in terms of the number of synapses at which it acts) neurotransmitter in the nervous systems of vertebrates and invertebrates. Transmission of excitatory stimuli in the brains of vertebrates and in the neuromuscular system of arthropods is mediated by activation of postsynaptic glutamate receptors of the ionotropic type, i.e., receptors which are ligand-controlled ion channels. The interaction of glutamate with the recognition site on the extracellular side of the receptor converts the channel, for a short period of time, into the open state, this being the basis of the generation of the excitatory postsynaptic potential.
[Structural characteristics of ionotropic glutamate receptors revealed by channel blockade]
Rossiĭskii fiziologicheskiĭ zhurnal imeni I.M. Sechenova / Rossiĭskaia akademiia nauk
Glutamate is far from the only (in terms of the number of synapses at which it acts) neurotransmitter in the nervous systems of vertebrates and invertebrates. Transmission of excitatory stimuli in the brains of vertebrates and in the neuromuscular system of arthropods is mediated by activation of postsynaptic glutamate receptors of the ionotropic type, i.e., receptors which are ligand-controlled ion channels. The interaction of glutamate with the recognition site on the extracellular side of the receptor converts the channel, for a short period of time, into the open state, this being the basis of the generation of the excitatory postsynaptic potential.