Mutations in a putative agonist binding region of the AMPA-selective glutamate receptor channel.
The region preceding putative transmembrane segment M1 of the glutamate receptor (GluR) channel is well conserved among subunits and has been proposed to constitute a part of the agonist binding site. The functional significance of this region was examined by introducing point mutations into charged residues of the alpha 1 subunit of the mouse alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective GluR channel. The dose-response relationships of the mutant receptors were studied after expression in Xenopus oocytes by injection of the mutant alpha 1 subunit-specific mRNA together with the wild-type alpha 2-subunit-specific mRNA. Variable changes in the EC50 values for different agonists were found for the replacement of glutamic acid 398 by lysine and for the replacement of lysine 445 by glutamic acid. These residues may be involved in selective interaction of the GluR channel with agonists.
Uchino
S
S
Biosciences Laboratory, Mitsubishi Kasei Corporation, Yokohama, Japan.
Sakimura
K
K
Nagahari
K
K
Mishina
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D005971:Glutamates / Q000378:metabolism; D007051:Ibotenic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes; D016318:Quisqualic Acid / Q000378:metabolism; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; D007051:Ibotenic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D007608:Kainic Acid