Laube B, Kuryatov A, Kuhse J, Betz H
Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Frankfurt/M., Germany.
FEBS Lett. 1993 Dec 13;335(3):331-4. doi: 10.1016/0014-5793(93)80412-n.
The NMDA subtype of ionotropic glutamate receptors occupation by both L-glutamate and the co-agonist glycine for efficient channel opening. To elucidate the role of disulfide bridges for the allosteric interaction of these agonists we mutated the cysteine residues in the ligand-binding NMDAR1 (NR1 or zeta) subunit of the rodent NMDA receptor and co-expressed the resulting mutants with the NR2B (epsilon 2) subunit in Xenopus oocytes. Most of the cysteine substitutions had no effect on agonist responses. However, replacement of cysteines 402 and 418 by alanine largely abolished the potentiation of glutamate currents by glycine. These cysteine residues in the putative extracellular domain of the NR1 subunit may form a disulfide bridge important for agonist interaction.
离子型谷氨酸受体的NMDA亚型需要L-谷氨酸和共激动剂甘氨酸同时占据才能有效打开通道。为了阐明二硫键在这些激动剂变构相互作用中的作用，我们对啮齿动物NMDA受体的配体结合NMDAR1（NR1或ζ）亚基中的半胱氨酸残基进行了突变，并在非洲爪蟾卵母细胞中将所得突变体与NR2B（ε2）亚基共表达。大多数半胱氨酸替代对激动剂反应没有影响。然而，用丙氨酸取代半胱氨酸402和418在很大程度上消除了甘氨酸对谷氨酸电流的增强作用。NR1亚基假定的细胞外结构域中的这些半胱氨酸残基可能形成了对激动剂相互作用很重要的二硫键。
