Retinal Flip in Rhodopsin Activation?
Retinal Flip in Rhodopsin Activation?
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DOI：
10.1016/j.bpj.2015.04.040
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发表时间：
2015-06-16
影响因子：
3.4
通讯作者：
Mertz, Blake
中科院分区：
文献类型：
--
作者：
Feng, Jun;Brown, Michael F.;Mertz, Blake
视紫红质是G蛋白偶联受体的良好表征的结构模型。共价结合的视黄醛的光异构化触发激活。令人惊讶的是，活性间-II态的X射线晶体结构具有围绕视网膜多烯链的长轴的180度旋转。无偏微秒时间尺度的全原子分子动力学模拟表明，视网膜辅因子可以翻转回视紫红质的非活性状态下观察到的取向有利于Meta-I状态的条件下。据我们所知，我们的研究结果提供了分子动力学模拟的第一个证据，显示了视网膜配体在其结合口袋内的旋转如何发生在视紫红质的激活机制中。
Rhodopsin is a well-characterized structural model of a G protein-coupled receptor. Photoisomerization of the covalently bound retinal triggers activation. Surprisingly, the x-ray crystal structure of the active Meta-II state has a 180 degrees rotation about the long-axis of the retinal polyene chain. Unbiased microsecond-timescale all-atom molecular dynamics simulations show that the retinal cofactor can flip back to the orientation observed in the inactive state of rhodopsin under conditions favoring the Meta-I state. Our results provide, to our knowledge, the first evidence from molecular dynamics simulations showing how rotation of the retinal ligand within its binding pocket can occur in the activation mechanism of rhodopsin.