Structure of the NMDA receptor channel M2 segment inferred from the accessibility of substituted cysteines.
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.
Kuner
T
T
Zentrum für Molekulare Biologie, der Universität Heidelberg (ZMBH), Federal Republic of Germany.
Wollmuth
L P
LP
Karlin
A
A
Seeburg
P H
PH
Sakmann
B
B
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
D007202:Indicators and Reagents; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C093171:methanethiosulfonate ethylammonium; D005020:Ethyl Methanesulfonate; D003545:Cysteine