Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, London, SW7 2AZ, United Kingdom. Electronic address: https://twitter.com/@EmmaCouves.
Department of Life Sciences, Imperial College London, Sir Ernst Chain Building, London, SW7 2AZ, United Kingdom.
Curr Opin Struct Biol. 2022 Aug;75:102401. doi: 10.1016/j.sbi.2022.102401. Epub 2022 Jun 11.
Deployed by both pathogenic bacteria and host immune systems, pore-forming proteins rupture target membranes and can serve as conduits for effector proteins. Understanding how these proteins work relies on capturing assembly intermediates. Advances in cryoEM allowing in silico purification of heterogeneous assemblies has led to new insights into two main classes of pore-forming proteins: membrane attack complex perforin (MACPF) proteins and binary toxins. The structure of an immune activation complex, sMAC, shows how pores form by sequential templating and insertion of β-hairpins. CryoEM structures of bacterial binary toxins present a series of transitions along the pore formation pathway and reveal a general mechanism of effector protein translocation. Future developments in time-resolved cryoEM could capture and place short-lived states along the trajectory of pore-formation.
孔形成蛋白由病原细菌和宿主免疫系统共同部署，可破坏靶膜，并作为效应蛋白的通道。理解这些蛋白的工作机制依赖于捕获组装中间体。冷冻电镜技术的进步使得对异质组装体的计算机纯化成为可能，这为两类主要的孔形成蛋白（膜攻击复合物穿孔素（MACPF）蛋白和二元毒素）提供了新的见解。免疫激活复合物 sMAC 的结构显示了如何通过顺序模板化和β发夹的插入来形成孔。细菌二元毒素的冷冻电镜结构呈现了沿孔形成途径的一系列转变，并揭示了效应蛋白易位的一般机制。时间分辨冷冻电镜的未来发展可以沿孔形成轨迹捕获和定位短暂状态。
