X-rays in the Cryo-Electron Microscopy Era: Structural Biology’s Dynamic Future,Biochemistry

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X-rays in the Cryo-Electron Microscopy Era: Structural Biology’s Dynamic Future
Biochemistry ( IF 2.9 ) Pub Date : 2018-01-11 00:00:00 , DOI: 10.1021/acs.biochem.7b01031
Susannah C Shoemaker ₁ , Nozomi Ando ₁

Affiliation

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 kilodaltons 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 at 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.

中文翻译：

冷冻电子显微镜时代的 X 射线：结构生物学的动态未来

在过去的几年中，单粒子冷冻电子显微镜 (cryo-EM) 已成为以近原子分辨率阐明大分子结构的领先方法，甚至可以与现有的 X 射线晶体学技术相媲美。冷冻电镜现在能够探测像血红蛋白 (64 kDa) 这样小的蛋白质，同时完全避免结晶瓶颈。冷冻电镜的巨大成功让人们对 X 射线方法（尤其是晶体学）的持续相关性产生了质疑。然而，如果说结构生物学的未来要么是冷冻电镜，要么是晶体学，这是错误的。晶体学仍然更适合产生数百道尔顿以下大分子的精确原子坐标，而探测更大、可能更无序的组装体的能力是冷冻电镜的明显优势。同样，晶体学能够更好地提供作为时间、温度、压力和其他扰动的函数的高分辨率动态信息，而冷冻电镜可以提供对构象和能量景观的越来越深入的了解，特别是随着解卷积构象异质性的算法变得更加先进。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。结构测定只是一个更大难题的一小部分：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 射线方法和冷冻电镜可以塑造结构生物学未来的独特且互补的方式。

更新日期：2018-01-11

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