Maltsev Alexander S, Ahmed Ahmed H, Fenwick Michael K, Jane David E, Oswald Robert E
Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA.
Biochemistry. 2008 Oct 7;47(40):10600-10. doi: 10.1021/bi800843c. Epub 2008 Sep 17.
The mechanism by which the binding of a neurotransmitter to a receptor leads to channel opening is a central issue in molecular neurobiology. The structure of the agonist binding domain of ionotropic glutamate receptors has led to an improved understanding of the changes in structure that accompany agonist binding and have provided important clues about the link between these structural changes and channel activation and desensitization. However, because the binding domain has exhibited different structures under different crystallization conditions, understanding the structure in the absence of crystal packing is of considerable importance. The orientation of the two lobes of the binding domain in the presence of a full agonist, an antagonist, and several partial agonists was measured using NMR spectroscopy by employing residual dipolar couplings. For some partial agonists, the solution conformation differs from that observed in the crystal. A model of channel activation based on the results is discussed.
神经递质与受体结合导致通道开放的机制是分子神经生物学的核心问题。离子型谷氨酸受体激动剂结合结构域的结构增进了我们对激动剂结合时伴随的结构变化的理解，并为这些结构变化与通道激活和脱敏之间的联系提供了重要线索。然而，由于结合结构域在不同的结晶条件下呈现出不同的结构，因此了解无晶体堆积情况下的结构具有相当重要的意义。通过使用残余偶极耦合的核磁共振光谱法，测量了在存在完全激动剂、拮抗剂和几种部分激动剂的情况下结合结构域两个叶的取向。对于一些部分激动剂，溶液构象与晶体中观察到的不同。基于这些结果讨论了通道激活模型。
