Cryo-Electron Microscopy, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
The Division of Structural Biology, Wellcome Centre for Human Genetics, The University of Oxford, Oxford, UK.
J Neurochem. 2021 Sep;158(6):1236-1243. doi: 10.1111/jnc.15245. Epub 2020 Dec 10.
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) exist in a variety of oligomeric forms, each with defined cellular and subcellular distributions. Although crystal structures of AChE and BChE have been available for many years, structures of the physiologically relevant ChE tetramer were only recently solved by cryo-electron microscopy (cryo-EM) single-particle analysis. Here, we briefly review how these structures contribute to our understanding of cholinesterase oligomerization, highlighting the advantages of using cryo-EM to resolve structures of protein assemblies that cannot be expressed recombinantly. We argue that the next frontier in cholinesterase structural biology is to image membrane-anchored ChE oligomers directly in their native environment-the cell.
乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BChE) 以多种寡聚体形式存在，每种形式都具有特定的细胞和亚细胞分布。尽管 AChE 和 BChE 的晶体结构已经存在多年，但最近才通过冷冻电镜 (cryo-EM) 单颗粒分析解决了生理相关的 ChE 四聚体的结构。在这里，我们简要回顾了这些结构如何帮助我们理解胆碱酯酶的寡聚化，强调了使用 cryo-EM 来解析无法通过重组表达的蛋白质组装结构的优势。我们认为，胆碱酯酶结构生物学的下一个前沿是直接在其天然环境——细胞中对膜锚定的 ChE 寡聚体进行成像。
