Characterizing the energetic states of the GluR2 ligand binding domain core-dimer.
Characterizing the energetic states of the GluR2 ligand binding domain core-dimer.
复制标题
表征 GluR2 配体结合域核心二聚体的能量状态。
DOI：
10.1016/j.bpj.2010.10.048
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发表时间：
2011
影响因子：
3.4
通讯作者：
Kurnikova,Maria
中科院分区：
文献类型：
--
作者：
Yonkunas,Michael;Kurnikova,Maria
离子型谷氨酸受体家族的四聚体配体结合域组装为二聚体的二聚体。对几种谷氨酸受体亚型分离的核心二聚体的晶体学研究表明单一稳定的二聚体构象。如果不借助生化方法破坏关键的二聚体界面，则无法以其他构象捕获结合域二聚体。分子动力学模拟和连续静电学计算表明，在典型晶体结构中发现的配体结合结构域的活性谷氨酸结合形式是在激动剂谷氨酸存在下分离的核心二聚体的首选能量状态。脱敏构象状态是核心二聚体的较高能量配体结合状态。静止apo构象状态是相对而言能量最不利的构象，并且不包含单一状态，而是包含一组能量等效的构象核心二聚体状态。我们假设必须包括开放跨膜区域与闭合跨膜区域的能量平衡来表征完整受体的绝对能量状态，在配体存在下，其被认为是脱敏状态。
Tetrameric ligand binding domains of the family of ionotropic glutamate receptors assemble as dimers-of-dimers. Crystallographic studies of several glutamate receptor subtype isolated core-dimers suggest a single stable dimeric conformation. A binding domain dimer has not been captured in other conformations without the aid of biochemical methods to disrupt a critical dimer interface. Molecular dynamics simulations and continuum electrostatics calculations reveal that the active glutamate bound form of the ligand-binding domain found in typical crystal structures is the preferred energetic state of the isolated core-dimer in the presence of agonist glutamate. A desensitized conformational state is a higher energy ligand-bound state of the core-dimer. The resting apo conformational state is comparatively the least energetically favored conformation and does not contain a single state but a set of energetically equivalent conformational core-dimer states. We hypothesize the energetic balance of an open versus closed transmembrane region must be included to characterize the absolute energetic states of the full receptor, which in the presence of the ligand is believed to be a desensitized state.