X-rays in the Cryo-Electron Microscopy Era: Structural Biology's Dynamic Future.
X-rays in the Cryo-Electron Microscopy Era: Structural Biology's Dynamic Future.
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DOI：
10.1021/acs.biochem.7b01031
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发表时间：
2018-01-23
期刊：
影响因子：
2.9
通讯作者：
Ando N
中科院分区：
文献类型：
--
作者：
Shoemaker SC;Ando N
在过去的几年中，单粒子低温电子显微镜（cryo-EM）已经成为以近原子分辨率阐明大分子结构的领先方法，甚至可以与X射线晶体学的既定技术相媲美。Cryo-EM现在能够探测小至血红蛋白（64 kDa）的蛋白质，同时完全避免了结晶瓶颈。cryo-EM的显著成功使人们对X射线方法的持续相关性提出了质疑，特别是晶体学。然而，如果说结构生物学的未来是冷冻电镜或结晶学，那就大错特错了。晶体学仍然更适合于产生精确的原子坐标的大分子在几百kDa的大小，而探测更大的能力，可能更无序的组件是一个明显的优势，冷冻EM。同样，晶体学更好地装备，以提供高分辨率的动态信息作为时间，温度，压力和其他扰动的函数，而cryo-EM提供越来越多的洞察构象和能量景观，特别是随着算法去卷积构象异质性变得更加先进。最终，这两种技术的未来取决于如何利用它们各自的优势来解决结构生物学的前沿问题。结构决定只是一个更大的难题的一部分：现代结构生物学的一个核心挑战是将结构信息与生物功能联系起来。从这个角度来看，我们分享了该领域几位领导者的见解，并研究了X射线方法和冷冻EM可以塑造结构生物学未来的独特和互补的方式。
Over the past several years, single-particle cryo-electron microscopy (cryo-EM) has emerged as a leading method for elucidating macromolecular structures at near-atomic resolution, rivaling even the established technique of X-ray crystallography. Cryo-EM is now able to probe proteins as small as hemoglobin (64 kDa), while avoiding the crystallization bottleneck entirely. The remarkable success of cryo-EM has called into question the continuing relevance of X-ray methods, particularly crystallography. To say that the future of structural biology is either cryo-EM or crystallography, however, would be misguided. Crystallography remains better suited to yield precise atomic coordinates of macromolecules under a few hundred kDa in size, while the ability to probe larger, potentially more disordered assemblies is a distinct advantage of cryo-EM. Likewise, crystallography is better equipped to provide high-resolution dynamic information as a function of time, temperature, pressure, and other perturbations, whereas cryo-EM offers increasing insight into conformational and energy landscapes, particularly as algorithms to deconvolute conformational heterogeneity become more advanced. Ultimately, the future of both techniques depends on how their individual strengths are utilized to tackle questions on the frontiers of structural biology. Structure determination is just one piece of a much larger puzzle: a central challenge of modern structural biology is to relate structural information to biological function. In this perspective, we share insight from several leaders in the field and examine the unique and complementary ways in which X-ray methods and cryo-EM can shape the future of structural biology.
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影响因子：
64.8
作者：
DEROSIER, DJ;KLUG, A
通讯作者：
KLUG, A
DOI：
10.1107/s010876738800354x
发表时间：
1988-07-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION A
影响因子：
--
作者：
BRICOGNE, G
通讯作者：
BRICOGNE, G
DOI：
10.1016/j.ymeth.2016.02.007
发表时间：
2016-05-01
期刊：
Methods (San Diego, Calif.)
影响因子：
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作者：
Frank J;Ourmazd A
通讯作者：
Ourmazd A
DOI：
10.1073/pnas.1002951107
发表时间：
2010-04-20
影响因子：
11.1
作者：
Cho, Hyun Sun;Dashdorj, Naranbaatar;Anfinrud, Philip
通讯作者：
Anfinrud, Philip
影响因子：
64.8
作者：
Dutta, Somnath;Whicher, Jonathan R.;Hansen, Douglas A.;Hale, Wendi A.;Chemler, Joseph A.;Congdon, Grady R.;Narayan, Alison R. H.;Hakansson, Kristina;Sherman, David H.;Smith, Janet L.;Skiniotis, Georgios
通讯作者：
Skiniotis, Georgios