Leschziner Andres E, Nogales Eva
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Annu Rev Biophys Biomol Struct. 2007;36:43-62. doi: 10.1146/annurev.biophys.36.040306.132742.
It is becoming increasingly clear that many macromolecules are intrinsically flexible and exist in multiple conformations in solution. Single-particle reconstruction of vitrified samples (cryo-electron microscopy, or cryo-EM) is uniquely positioned to visualize this conformational flexibility in its native state. Although heterogeneity remains a significant challenge in cryo-EM single-particle analysis, recent efforts in the field point to a future where it will be possible to tap into this rich source of biological information on a routine basis. In this article, we review the basic principles behind a few relatively new and generally applicable methods that show particular promise as tools to analyze macromolecular flexibility. We also discuss some of their recent applications to problems of biological interest.
越来越明显的是，许多大分子本质上是柔性的，并且在溶液中以多种构象存在。玻璃化样品的单颗粒重建（冷冻电子显微镜，即冷冻电镜）在可视化其天然状态下的这种构象柔性方面具有独特的优势。尽管异质性在冷冻电镜单颗粒分析中仍然是一个重大挑战，但该领域最近的努力表明，未来有可能在常规基础上利用这一丰富的生物信息来源。在本文中，我们回顾了一些相对较新且普遍适用的方法背后的基本原理，这些方法作为分析大分子柔性的工具显示出特别的前景。我们还讨论了它们最近在一些生物学相关问题上的应用。
