Continuous changes in structure mapped by manifold embedding of single-particle data in cryo-EM.
Continuous changes in structure mapped by manifold embedding of single-particle data in cryo-EM.
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DOI：
10.1016/j.ymeth.2016.02.007
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发表时间：
2016-05-01
期刊：
影响因子：
--
通讯作者：
Ourmazd A
中科院分区：
文献类型：
--
作者：
Frank J;Ourmazd A
冷冻电子显微镜与单粒子重建相结合，是研究大分子结构的有力方法。探测器技术的最新发展已经将分辨率推到了与X射线晶体学相当的范围内。然而，cryo-EM能够分离并因此恢复存在于样品中的若干离散结构中的每一个的结构。对于更一般的情况下，涉及连续的结构变化，一种新的技术，采用流形嵌入最近已被证明。潜在地，当分子机器通过连续状态时，它的整个工作周期可以被观察到，并且它的自由能景观可以被绘制出来。这种技术将概述和讨论的背景下，其应用到一个大的单粒子数据集的酵母核糖体。
Cryo-electron microscopy, when combined with single-particle reconstruction, is a powerful method for studying macromolecular structure. Recent developments in detector technology have pushed the resolution into a range comparable to that of X-ray crystallography. However, cryo-EM is able to separate and thus recover the structure of each of several discrete structures present in the sample. For the more general case involving continuous structural changes, a novel technique employing manifold embedding has been recently demonstrated. Potentially, the entire work-cycle of a molecular machine may be observed as it passes through a continuum of states, and its free-energy landscape may be mapped out. This technique will be outlined and discussed in the context of its application to a large single-particle dataset of yeast ribosomes.