Dynamics of the S1S2 glutamate binding domain of GluR2 measured using 19F NMR spectroscopy
Dynamics of the S1S2 glutamate binding domain of GluR2 measured using 19F NMR spectroscopy
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DOI：
10.1074/jbc.m610077200
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发表时间：
2007-04-27
影响因子：
4.8
通讯作者：
Oswald, Robert E.
中科院分区：
文献类型：
--
作者：
Ahmed, H. Ahmed;Loh, Adrienne P.;Oswald, Robert E.
嗜电性谷氨酸受体介导了大部分脊椎动物兴奋性突触传递。虽然GluR2结合域（S1S2）的结构是众所周知的（两叶之间的激动剂结合位点），但对构象转变的时间尺度或动力学与功能之间的关系知之甚少。（FNMR）-F-19 （f -19标记色氨酸）光谱用于监测不同功效和载脂蛋白状态下与配体结合的S1S2结构域的运动。一种色氨酸（色氨酸-671）在一些但不是所有的激动剂中进行化学交换，与mu - s-ms运动一致。该动力学可以与配体亲和力相关，并且该运动的一个可能来源是能够在叶状界面上瞬时形成氢键的肽键。另一种色氨酸（Trp767）似乎监测脑叶相对位置的运动，并表明载脂蛋白和拮抗剂结合形式的相对取向可以在ms时间尺度上在至少两种构象之间交换。
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. (FNMR)-F-19 (F-19-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 mu s-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 (Trp767) 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.