Molecular dynamics of protein complexes from four-dimensional cryo-electron microscopy
Molecular dynamics of protein complexes from four-dimensional cryo-electron microscopy
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DOI：
10.1016/j.jsb.2004.02.006
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发表时间：
2004-09-01
影响因子：
3
通讯作者：
Steven, AC
中科院分区：
文献类型：
--
作者：
Heymann, JB;Conway, JF;Steven, AC
单颗粒冷冻电子显微镜提供了一个独特的机会，检测和定量蛋白质复合物的构象变化。原则上，不同的构象异构体可以通过对单个投影的分类来区分，其中通过“多粒子分析”（MPA）将观察几何形状产生的图像差异与底层结构的变异性分开。如果不同的构象代表同一复合物的动态相关状态，MPA有可能可视化过渡状态，并最终产生动态过程的电影。如果从已知在时间上发展的系统在连续时间获取低温EM数据，则促进将各种构象异构体排序为时间序列。病毒成熟是一个相对容易处理的动态过程，因为变化很大且不可逆，并且可以通过调节环境条件在体外方便地减慢自然过程的速率。我们描述了最近的单纯疱疹病毒原衣壳成熟的分析（自然结构生物学10（2003）334-341）中采用的策略，将其与以前的噬菌体HK 97原衣壳成熟的工作进行比较，并讨论了在一般情况下进行类似的分子动力学实验分析的可行性的各种影响因素。爱思唯尔公司出版
Cryo-electron microscopy of single particles offers a unique opportunity to detect and quantify conformational variation of protein complexes. Different conformers may, in principle, be distinguished by classification of individual projections in which image differences arising from viewing geometry are disentangled from variability in the underlying structures by "multiple particle analysis"-MPA. If the various conformers represent dynamically related states of the same complex, MPA has the potential to visualize transition states, and eventually to yield movies of the dynamic process. Ordering the various conformers into a time series is facilitated if cryo-EM data are taken at successive times from a system that is known to be developing in time. Virus maturation represents a relatively tractable dynamic process because the changes are large and irreversible and the rate of the natural process may be conveniently slowed in vitro by adjusting the environmental conditions. We describe the strategy employed in a recent analysis of herpes simplex virus procapsid maturation (Nat. Struct. Biol. 10 (2003) 334-341), compare it with previous work on the maturation of bacteriophage HK97 procapsid, and discuss various factors that impinge on the feasibility of performing similar experimental analyses of molecular dynamics in the general case. Published by Elsevier Inc.