Balasuriya Dilshan, Takahashi Hirohide, Srivats Shyam, Edwardson J Michael
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, United Kingdom.
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1452-7. doi: 10.1016/j.bbrc.2014.07.009. Epub 2014 Jul 10.
Unlike GluN2-containing N-methyl-d-aspartate (NMDA) receptors, which require both glycine and glutamate for activation, receptors composed of GluN1 and GluN3 subunits are activated by glycine alone. Here, we used atomic force microscopy (AFM) imaging to examine the response to activation of the GluN1/GluN3A excitatory glycine receptor. GluN1 and GluN3A subunits were shown to interact intimately within transfected tsA 201 cells. Isolated GluN1/GluN3A receptors integrated into lipid bilayers responded to addition of either glycine or d-serine, but not glutamate, with a ∼1 nm reduction in height of the extracellular domain. The height reduction in response to glycine was abolished by the glycine antagonist 5,7-dichlorokynurenic acid. Our results represent the first demonstration of the effect of activation on the conformation of this receptor.
与含GluN2的N-甲基-D-天冬氨酸（NMDA）受体不同，后者需要甘氨酸和谷氨酸共同作用才能激活，而由GluN1和GluN3亚基组成的受体仅由甘氨酸激活。在此，我们使用原子力显微镜（AFM）成像来检测对GluN1/GluN3A兴奋性甘氨酸受体激活的反应。结果显示，GluN1和GluN3A亚基在转染的tsA 201细胞内紧密相互作用。整合到脂质双层中的分离的GluN1/GluN3A受体对添加甘氨酸或D-丝氨酸有反应，但对谷氨酸无反应，细胞外结构域高度降低约1 nm。甘氨酸拮抗剂5,7-二氯犬尿氨酸消除了对甘氨酸反应的高度降低。我们的结果首次证明了激活对该受体构象的影响。
