Birch James, Cheruvara Harish, Gamage Nadisha, Harrison Peter J, Lithgo Ryan, Quigley Andrew
Membrane Protein Laboratory, Diamond Light Source Ltd., Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.
Research Complex at Harwell (RCaH), Harwell Science and Innovation Campus, Didcot OX11 0FA, UK.
Biology (Basel). 2020 Nov 16;9(11):401. doi: 10.3390/biology9110401.
Membrane proteins are essential components of many biochemical processes and are important pharmaceutical targets. Membrane protein structural biology provides the molecular rationale for these biochemical process as well as being a highly useful tool for drug discovery. Unfortunately, membrane protein structural biology is a difficult area of study due to low protein yields and high levels of instability especially when membrane proteins are removed from their native environments. Despite this instability, membrane protein structural biology has made great leaps over the last fifteen years. Today, the landscape is almost unrecognisable. The numbers of available atomic resolution structures have increased 10-fold though advances in crystallography and more recently by cryo-electron microscopy. These advances in structural biology were achieved through the efforts of many researchers around the world as well as initiatives such as the Membrane Protein Laboratory (MPL) at Diamond Light Source. The MPL has helped, provided access to and contributed to advances in protein production, sample preparation and data collection. Together, these advances have enabled higher resolution structures, from less material, at a greater rate, from a more diverse range of membrane protein targets. Despite this success, significant challenges remain. Here, we review the progress made and highlight current and future challenges that will be overcome.
膜蛋白是许多生物化学过程的重要组成部分，也是重要的药物靶点。膜蛋白结构生物学为这些生物化学过程提供了分子理论依据，同时也是药物发现的一种非常有用的工具。不幸的是，由于蛋白质产量低和高度不稳定，尤其是当膜蛋白从其天然环境中分离出来时，膜蛋白结构生物学是一个困难的研究领域。尽管存在这种不稳定性，但在过去十五年中，膜蛋白结构生物学取得了巨大飞跃。如今，情况几乎面目全非。通过晶体学的进步以及最近的冷冻电子显微镜技术，可用的原子分辨率结构数量增加了10倍。这些结构生物学的进步是通过世界各地许多研究人员的努力以及诸如钻石光源的膜蛋白实验室（MPL）等倡议实现的。MPL在蛋白质生产、样品制备和数据收集方面提供了帮助、便利并推动了进展。这些进展共同使得能够以更高的分辨率、从更少的材料、以更快的速度、针对更多样化的膜蛋白靶点获得结构。尽管取得了这一成功，但重大挑战依然存在。在此，我们回顾所取得的进展，并突出当前和未来将被克服的挑战。
