title: Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines.
abstract: The structure of the NMDA receptor channel M2 segment was investigated by probing the extracellular and cytoplasmic faces of cysteine-substituted NR1-NR2C channels with charged sulfhydryl-specific reagents. The pattern of accessible positions suggests that the M2 segment forms a channel-lining loop originating and ending on the cytoplasmic side of the channel, with the ascending limb in an alpha-helical structure and the descending limb in an extended structure. A functionally critical asparagine (N-site) is positioned at the tip of the loop, and a cluster of hydrophilic residues of the descending limb, adjacent to the tip, forms the narrow constriction of the channel. An apparent asymmetric positioning of the NR1- and NR2-subunit N-site asparagines may account for their unequal role in Ca2+ permeability and Mg2+ block.
authors.affiliation: Zentrum für Molekulare Biologie, der Universität Heidelberg (ZMBH), Federal Republic of Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kuner
authors.forename: L P
authors.initials: LP
authors.lastname: Wollmuth
authors.forename: A
authors.initials: A
authors.lastname: Karlin
authors.forename: P H
authors.initials: PH
authors.lastname: Seeburg
authors.forename: B
authors.initials: B
authors.lastname: Sakmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine / Q000737:chemistry* / Q000235:genetics*; D003593:Cytoplasm / Q000737:chemistry; D005020:Ethyl Methanesulfonate / Q000031:analogs & derivatives / Q000494:pharmacology; D005110:Extracellular Space / Q000737:chemistry; D005260:Female; D007202:Indicators and Reagents / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000235:genetics*; D014982:Xenopus laevis
chemical_list: D007202:Indicators and Reagents; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C093171:methanethiosulfonate ethylammonium; D005020:Ethyl Methanesulfonate; D003545:Cysteine