Family 1.A.10 - The Glutamate-gated Ion Channel Family        

Family ID: 52599

Eukaryotic members of the GIC family are thought to be heteropentameric complexes in which each of the 5 subunits is of 800-1000 amino acyl residues in length. These subunits may span the membrane three or five times as putative a-helices with the N-termini (the glutamate-binding domains) localized extracellularly and the C-termini localized cytoplasmically. They may be distantly related to the ligand-gated ion channels (LIC; TC #1.A.10), and if so, they may possess substantial b?structure in their transmembrane regions. However, homology between these two families cannot be established on the basis of sequence comparisons alone. The subunits fall into six subfamilies: a, b, g, d, e and z.

The GIC channels are divided into three types: (1) a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-, (2) kainate- and (3) N-methyl-D-aspartate (NMDA)-selective glutamate receptors. Subunits of the AMPA and kainate classes exhibit 35-40% identity with each other while subunits of the NMDA receptors exhibit 22-24% identity with the former subunits. They possess large N-terminal, extracellular glutamate-binding domains that are homologous to the periplasmic glutamine and glutamate receptors (TC #3.A.1.3.2 and TC #3.A.1.3.4, respectively) of ABC-type uptake permeases (TC #3.A.1) of Gram-negative bacteria. All known members of the GIC family are from animals. The different channel (receptor) types exhibit distinct ion selectivities and conductance properties. The NMDA-selective large conductance channels are highly permeable to monovalent cations and Ca2+. The AMPA- and kainate-selective ion channels are permeable primarily to monovalent cations with only low permeability to Ca2+.

A K+-selective glutamate receptor that binds glutamate and forms K+-selective ion channels has recently been characterized (Chen et al., 1999). It shows sequence similarity to both glutamate receptors of eukaryotes and to K+ channels of the VIC family (TC #1.A.1). It exhibits 397 amino acyl residues, a signal peptide, and three TMSs flanked by two regions of about 140 residues. It showed highest sequence similarity to the rat d1 GluR followed by a putative GluR from Arabidopsis thaliana. As a result of these observations, it has been proposed that glutamate receptors of eukaryotes are tetramers, and that they arose from a primordial prokaryotic protein (Chen et al., 1999).