Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
Nanoscale. 2018 Jul 9;10(26):12256-12267. doi: 10.1039/c8nr02867b.
Macromolecular phase transitions bear great medical, scientific and industrial relevance, yet the molecular picture of their earliest beginnings is still far from complete. For decades, progress has been hampered by the challenges associated with studying stochastic nucleation phenomena occurring on nanoscopic length scales. In the last 5 years, however, the field has advanced with great strides due to the recent buildout of experimental techniques that allow us to observe details of the nucleation process on the nanoscale. In this review, we present a historical overview and state-of-the-art analysis of protein crystal nucleation from an experimentalist's perspective. After a short introduction of key concepts from classical nucleation theory, we discuss the advancements that have led to the development of alternative models of protein nucleation. We summarize the experimental proof in favour of these various models, but we also focus on some of their shortcomings and experimental blind spots. In our penultimate section we highlight recent works that have provided direct nanoscopic insight into the nucleation of protein crystals. We end with concluding paragraphs discussing outstanding questions and possible strategies to advance the field further in the future.
大分子相转变具有重要的医学、科学和工业意义，但它们最早起源的分子图景仍然远未完成。几十年来，由于研究发生在纳米尺度上的随机成核现象相关的挑战，进展一直受到阻碍。然而，在过去的 5 年中，由于最近开发出了允许我们在纳米尺度上观察成核过程细节的实验技术，该领域取得了巨大的进展。在这篇综述中，我们从实验的角度展示了蛋白质晶体成核的历史概述和最新分析。在简要介绍经典成核理论的关键概念之后，我们讨论了促成替代蛋白质成核模型发展的进展。我们总结了支持这些不同模型的实验证据，但我们也关注了它们的一些缺点和实验盲点。在倒数第二段中，我们重点介绍了最近的一些研究工作，这些研究工作为蛋白质晶体成核提供了直接的纳米尺度见解。最后，我们在结束语部分讨论了悬而未决的问题和未来可能的策略，以进一步推动该领域的发展。
