ZoeGene Corporation, Yokohama, Kanagawa, Japan.
Biophys Chem. 2012 Mar;162:35-44. doi: 10.1016/j.bpc.2011.12.004. Epub 2011 Dec 28.
The gating of ion channel of ionotropic glutamate receptors is controlled by the structural change of the ligand-binding domain of GluR2. We examined the roles of residues in the glutamate-binding and cleft-closing mechanisms by molecular dynamics (MD) simulations. A glutamate entered the cleft deeply within the order of nanoseconds and the cleft locked the glutamate completely at 15 ns in an MD run. TYR450 seemed to regulate the orientation of the glutamate upon binding by cation-π interaction. A semi-open state was identified in the free energy profile evaluated with the structures on the spontaneously glutamate-bound and cleft-closed pathway by the unbiased MD simulations for the first time to our knowledge. In the semi-open state, the two sub-domains were bridged by two hydrogen bonds of GLU705 in the sub-domain 2 with TYR732 in the sub-domain 1 and with the glutamate bound to the sub-domain 1 until the transition to the closed state.
离子型谷氨酸受体的离子通道门控由 GluR2 配体结合域的结构变化控制。我们通过分子动力学 (MD) 模拟研究了残基在谷氨酸结合和裂隙关闭机制中的作用。谷氨酸在纳秒级的顺序深入到裂隙中，在 MD 运行的 15 ns 时裂隙完全锁定谷氨酸。TYR450 通过阳离子-π 相互作用似乎调节了结合时谷氨酸的取向。在无偏 MD 模拟中，我们首次在结构上评估了自由能曲线，发现了一个自发结合谷氨酸和裂隙关闭途径上的半开放状态。在半开放状态下，两个亚域通过亚域 2 中的 GLU705 与亚域 1 中的 TYR732 之间的两个氢键以及与结合到亚域 1 的谷氨酸桥接，直到过渡到关闭状态。
