Intersubunit cooperativity in the NMDA receptor.
Opening of the NMDA receptor channel requires simultaneous binding of glutamate and glycine. Although the binding sites for each agonist are in different subunits, the presence of one agonist influences the binding of the other. We have localized regions in the S1 binding domain of both subunits required for the transmission of allosteric signals from the glutamate binding NR2A subunit to the glycine binding NR1 subunit. Three-dimensional modeling indicates that these segments are not directly involved in ligand binding, but likely form solvent-accessible loops protruding out of the binding pocket, making them suitable to relay interactions between adjacent subunits. Thus, these segments mediate negative allosteric coupling between the two subunit types that form the NMDA receptor.
Regalado
M P
MP
Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002, Madrid, Spain.
Villarroel
A
A
Lerma
J
J
D000494:Allosteric Regulation / Q000502:physiology; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D002460:Cell Line; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007668:Kidney / Q000166:cytology; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005998:Glycine