Ahmed Ahmed H, Loh Adrienne P, Jane David E, Oswald Robert E
Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA.
J Biol Chem. 2007 Apr 27;282(17):12773-84. doi: 10.1074/jbc.M610077200. Epub 2007 Mar 2.
Ionotropic glutamate receptors mediate the majority of vertebrate excitatory synaptic transmission. Although the structure of the GluR2 binding domain (S1S2) is well known (agonist binding site between two lobes), little is known about the time scales of conformational transitions or the relationship between dynamics and function. (19)F NMR ((19)F-labeled tryptophan) spectroscopy was used to monitor motions in the S1S2 domain bound to ligands with varying efficacy and in the apo state. One tryptophan (Trp-671) undergoes chemical exchange in some but not all agonists, consistent with mus-ms motion. The dynamics can be correlated to ligand affinity, and a likely source of the motion is a peptide bond capable of transiently forming hydrogen bonds across the lobe interface. Another tryptophan (Trp-767) appears to monitor motions of the relative positions of the lobes and suggests that the relative orientation in the apo- and antagonist-bound forms can exchange between at least two conformations on the ms time scale.
离子型谷氨酸受体介导了大多数脊椎动物的兴奋性突触传递。尽管谷氨酸受体2结合域（S1S2）的结构已为人熟知（两个叶之间的激动剂结合位点），但对于构象转变的时间尺度或动力学与功能之间的关系却知之甚少。利用（19）F核磁共振（（19）F标记的色氨酸）光谱来监测与具有不同效力的配体结合的S1S2结构域以及无配体状态下的运动。一个色氨酸（Trp-671）在一些但并非所有激动剂中发生化学交换，这与微秒到毫秒级的运动一致。动力学可以与配体亲和力相关联，并且这种运动的一个可能来源是一个能够在叶界面上短暂形成氢键的肽键。另一个色氨酸（Trp-767）似乎监测叶相对位置的运动，并表明在无配体和拮抗剂结合形式中的相对取向可以在毫秒时间尺度上在至少两种构象之间交换。
