Ishida Hisashi, Hayward Steven
Quantum Beam Science Directorate and Center for Computational Science and e-Systems, Japan Atomic Energy Agency, Kyoto 619-0215, Japan.
Biophys J. 2008 Dec 15;95(12):5962-73. doi: 10.1529/biophysj.108.134890. Epub 2008 Oct 20.
Molecular dynamics simulations were carried out on Thermus thermophilus 70S ribosome with and without a nascent polypeptide inside the exit tunnel. Modeling of the polypeptide in the tunnel revealed two possible paths: one over Arg92 of L22 and one under (from the viewpoint of 50S on top of 30S). A strong interaction between L4 and Arg92 was observed without the polypeptide and when it passed over Arg92. However, when the polypeptide passed under, Arg92 repositioned to interact with Ade2059 of 23S rRNA. Using steered molecular dynamics the polypeptide could be pulled through the L4-L22 constriction when situated under Arg92, but did not move when over. These results suggest that the tunnel is closed by the Arg92-L4 interaction before elongation of the polypeptide and the tunnel leads the entering polypeptide from the peptidyl transferase center to the passage under Arg92, causing Arg92 to switch to an open position. It is possible, therefore, that Arg92 plays the role of a gate, opening and closing the tunnel at L4-L22. There is some disagreement over whether the tunnel is dynamic or rigid. At least within the timescale of our simulations conformational analysis showed that global motions mainly involve relative movement of the 50S and 30S subunits and seem not to affect the conformation of the tunnel.
对嗜热栖热菌70S核糖体进行了分子动力学模拟，该核糖体的出口通道内有无新生多肽。对通道内多肽的建模揭示了两条可能的路径：一条在L22的Arg92上方，另一条在下方（从30S上方的50S角度看）。在没有多肽时以及多肽从Arg92上方通过时，观察到L4与Arg92之间有强烈的相互作用。然而，当多肽从下方通过时，Arg92重新定位以与23S rRNA的Ade2059相互作用。使用引导分子动力学，当多肽位于Arg92下方时可以将其拉过L4-L22收缩处，但当位于上方时则不会移动。这些结果表明，在多肽延伸之前，通道被Arg92-L4相互作用关闭，通道将进入的多肽从肽基转移酶中心引导至Arg92下方的通道，导致Arg92切换到开放位置。因此，Arg92有可能起到门的作用，在L4-L22处打开和关闭通道。关于通道是动态的还是刚性的存在一些分歧。至少在我们模拟的时间尺度内，构象分析表明全局运动主要涉及50S和30S亚基的相对运动，似乎不影响通道的构象。
