Trajectories of the ribosome as a Brownian nanomachine
Trajectories of the ribosome as a Brownian nanomachine
复制标题
DOI：
10.1073/pnas.1419276111
复制
发表时间：
2014-12-09
影响因子：
11.1
通讯作者：
Ourmazd, Abbas
中科院分区：
文献类型：
--
作者：
Dashti, Ali;Schwander, Peter;Ourmazd, Abbas
布朗机器是一种受到环境中分子随机运动影响的微型设备，能够利用这些热运动来实现其工作周期中的许多构象变化。现在人们认为这种机器无处不在，核糖体（一种负责蛋白质合成的分子机器）越来越被视为原型。在这里，我们提出了一种新的分析方法，能够从低温电子显微镜获得的大量快照中确定分子机器的自由能景观和连续轨迹。我们在从酵母细胞纯化的大量非翻译核糖体的实验低温电子显微镜图像的背景下证明了这种方法。自由能景观被认为包含一条闭合的低能量路径，沿着该路径核糖体表现出已知与延伸循环相关的构象变化。我们的方法允许对纳米机器中连续构象变化背后的自由度和能量景观进行无模型定量分析，包括那些对生物功能重要的变化。
A Brownian machine, a tiny device buffeted by the random motions of molecules in the environment, is capable of exploiting these thermal motions for many of the conformational changes in its work cycle. Such machines are now thought to be ubiquitous, with the ribosome, a molecular machine responsible for protein synthesis, increasingly regarded as prototypical. Here we present a new analytical approach capable of determining the free-energy landscape and the continuous trajectories of molecular machines from a large number of snapshots obtained by cryogenic electron microscopy. We demonstrate this approach in the context of experimental cryogenic electron microscope images of a large ensemble of nontranslating ribosomes purified from yeast cells. The free-energy landscape is seen to contain a closed path of low energy, along which the ribosome exhibits conformational changes known to be associated with the elongation cycle. Our approach allows model-free quantitative analysis of the degrees of freedom and the energy landscape underlying continuous conformational changes in nanomachines, including those important for biological function.