Energy barriers and driving forces in tRNA translocation through the ribosome
Energy barriers and driving forces in tRNA translocation through the ribosome
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DOI：
10.1038/nsmb.2690
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发表时间：
2013-12-01
影响因子：
16.8
通讯作者：
Grubmueller, Helmut
中科院分区：
文献类型：
--
作者：
Bock, Lars V.;Blau, Christian;Grubmueller, Helmut
在蛋白质合成过程中，trna从核糖体的氨基基到肽基移动到退出位点。在这里，我们研究了自发易位过程中的构象运动，利用分子动力学模拟了13个中间易位状态模型，这些模型是由大肠杆菌核糖体晶体结构和低温电镜数据相结合得到的。通过解决状态之间的快速转换，我们发现tRNA运动控制着易位前后状态的转换速率。亚基间旋转和l1 -柄运动表现出快速的内在亚微秒动力学。L1柄驱动tRNA离开肽基位点，并连接亚基间旋转和易位。tRNA的位移由涉及保守的L16、L5和L1残基的“滑动”和“步进”机制控制，从而确保在tRNA大规模移动的情况下与核糖体结合。我们的研究结果补充了结构数据，包括时间轴、固有跃迁率和分子力，揭示了其他方法无法获得的相关功能运动。
During protein synthesis, tRNAs move from the ribosome's aminoacyl to peptidyl to exit sites. Here we investigate conformational motions during spontaneous translocation, using molecular dynamics simulations of 13 intermediate-translocation-state models obtained by combining Escherichia coli ribosome crystal structures with cryo-EM data. Resolving fast transitions between states, we find that tRNA motions govern the transition rates within the pre- and post-translocation states. Intersubunit rotations and L1-stalk motion exhibit fast intrinsic submicrosecond dynamics. The L1 stalk drives the tRNA from the peptidyl site and links intersubunit rotation to translocation. Displacement of tRNAs is controlled by 'sliding' and 'stepping' mechanisms involving conserved L16, L5 and L1 residues, thus ensuring binding to the ribosome despite large-scale tRNA movement. Our results complement structural data with a time axis, intrinsic transition rates and molecular forces, revealing correlated functional motions inaccessible by other means.