Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Ratzeburger Allee 160, D-23562 Lübeck, Germany.
Deutsches Elektronen Synchrotron (DESY), Notkestrasse 85, D-22607 Hamburg, Germany.
Biol Chem. 2018 Jun 27;399(7):751-772. doi: 10.1515/hsz-2018-0158.
Protein crystallization in living cells has been observed surprisingly often as a native assembly process during the past decades, and emerging evidence indicates that this phenomenon is also accessible for recombinant proteins. But only recently the advent of high-brilliance synchrotron sources, X-ray free-electron lasers, and improved serial data collection strategies has allowed the use of these micrometer-sized crystals for structural biology. Thus, in cellulo crystallization could offer exciting new possibilities for proteins that do not crystallize applying conventional approaches. In this review, we comprehensively summarize the current knowledge of intracellular protein crystallization. This includes an overview of the cellular functions, the physical properties, and, if known, the mode of regulation of native in cellulo crystal formation, complemented with a discussion of the reported crystallization events of recombinant proteins and the current method developments to successfully collect X-ray diffraction data from in cellulo crystals. Although the intracellular protein self-assembly mechanisms are still poorly understood, regulatory differences between native in cellulo crystallization linked to a specific function and accidently crystallizing proteins, either disease associated or recombinantly introduced, become evident. These insights are important to systematically exploit living cells as protein crystallization chambers in the future.
在过去的几十年中，人们惊讶地发现，蛋白质在活细胞中的结晶经常作为一种天然的组装过程出现，而且新出现的证据表明，这种现象也适用于重组蛋白。但是，直到最近，高亮度同步加速器源、X 射线自由电子激光器和改进的连续数据采集策略的出现，才使得这些微米大小的晶体能够用于结构生物学。因此，在细胞内结晶可能为那些采用传统方法无法结晶的蛋白质提供令人兴奋的新可能性。在这篇综述中，我们全面总结了目前对细胞内蛋白质结晶的认识。这包括对细胞内天然晶体形成的细胞功能、物理性质的概述，如果已知的话，还包括对其调控模式的讨论，以及对重组蛋白报道的结晶事件和目前成功收集细胞内晶体 X 射线衍射数据的方法发展的讨论。尽管细胞内蛋白质自组装机制仍知之甚少，但与特定功能相关的天然细胞内结晶的调控差异，以及与疾病相关或重组引入的偶然结晶蛋白质之间的差异变得明显。这些见解对于未来系统地利用活细胞作为蛋白质结晶室是很重要的。
