A single tryptophan on M2 of glutamate receptor channels confers high permeability to divalent cations.
Ionotropic glutamate receptors (iGluRs) of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate subtype display lower permeability to Ca2+ than the N-methyl-D-aspartate (NMDA) subtype. The well-documented N/Q/R site on the M2 transmembrane segment (M2) is an important determinant of the distinct Ca2+ permeability exhibited by members of the non-NMDA receptor subfamily. This site, however, does not completely account for the different permeation properties displayed by non-NMDA and NMDA receptors, suggesting the involvement of other molecular determinants. We have identified additional molecular elements on M2 of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate/kainate receptor GluR1 that specify its permeation properties. Higher permeability to divalent over monovalent cations is conferred on GluR1 by a tryptophan at position 577, whereas blockade by external divalent cations is imparted by an asparagine at position 582. Hence, the permeation properties of ionotropic glutamate receptors appear to be primarily specified by two distinct determinants on M2, the well-known N/Q/R site and the newly identified L/W site. These findings substantiate the notion that M2 is a structural component of the pore lining.
Ferrer-Montiel
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AV
Department of Biology, University of California San Diego, La Jolla 92093-0366, USA.
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Montal
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D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism*; D002463:Cell Membrane Permeability; D018076:DNA, Complementary; D005260:Female; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology*; D017354:Point Mutation; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology; D017470:Receptors, Glutamate / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014364:Tryptophan; D014981:Xenopus
D002118:Calcium; D002413:Cations, Divalent; D018076:DNA, Complementary; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D014364:Tryptophan