MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK.
FEBS Lett. 2021 Nov;595(21):2691-2700. doi: 10.1002/1873-3468.14199. Epub 2021 Oct 18.
In bacteria, Lon is a large hexameric ATP-dependent protease that targets misfolded and also folded substrates, some of which are involved in cell division and survival of cellular stress. The N-terminal domain of Lon facilitates substrate recognition, but how the domains confer such activity has remained unclear. Here, we report the full-length structure of Lon protease from Thermus thermophilus at 3.9 Å resolution in a substrate-engaged state. The six N-terminal domains are arranged in three pairs, stabilized by coiled-coil segments and forming an additional channel for substrate sensing and entry into the AAA+ ring. Sequence conservation analysis and proteolysis assays confirm that this architecture is required for the degradation of both folded and unfolded substrates in bacteria.
在细菌中，Lon 是一种大型六聚体 ATP 依赖性蛋白酶，可靶向错误折叠和折叠的底物，其中一些与细胞分裂和细胞应激生存有关。Lon 的 N 端结构域有助于底物识别，但各结构域如何赋予这种活性尚不清楚。在这里，我们报告了 Thermus thermophilus Lon 蛋白酶全长结构在底物结合状态下的 3.9Å 分辨率。六个 N 端结构域以三对的形式排列，由螺旋-卷曲片段稳定，并形成用于底物感应和进入 AAA+环的附加通道。序列保守性分析和蛋白水解实验证实，这种结构对于细菌中折叠和未折叠底物的降解都是必需的。
