Li Yiying, Zhu Jie, Zhang Zhiyin, Wei Jiapeng, Wang Fengbin, Meisl Georg, Knowles Tuomas P J, Egelman Edward H, Tezcan F Akif
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, USA.
Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Nat Chem Biol. 2025 Jan 13. doi: 10.1038/s41589-024-01811-1.
Nucleoside triphosphate (NTP)-dependent protein assemblies such as microtubules and actin filaments have inspired the development of diverse chemically fueled molecular machines and active materials but their functional sophistication has yet to be matched by design. Given this challenge, we asked whether it is possible to transform a natural adenosine 5'-triphosphate (ATP)-dependent enzyme into a dissipative self-assembling system, thereby altering the structural and functional mode in which chemical energy is used. Here we report that FtsH (filamentous temperature-sensitive protease H), a hexameric ATPase involved in membrane protein degradation, can be readily engineered to form one-dimensional helical nanotubes. FtsH nanotubes require constant energy input to maintain their integrity and degrade over time with the concomitant hydrolysis of ATP, analogous to natural NTP-dependent cytoskeletal assemblies. Yet, in contrast to natural dissipative systems, ATP hydrolysis is catalyzed by free FtsH protomers and FtsH nanotubes serve to conserve ATP, leading to transient assemblies whose lifetimes can be tuned from days to minutes through the inclusion of external ATPases in solution.
诸如微管和肌动蛋白丝等依赖核苷三磷酸（NTP）的蛋白质组装体激发了多种化学驱动分子机器和活性材料的发展，但其功能复杂性尚未通过设计得以匹配。面对这一挑战，我们提出疑问：是否有可能将一种天然的依赖腺苷5'-三磷酸（ATP）的酶转化为一个耗散性自组装系统，从而改变利用化学能的结构和功能模式。在此我们报告，FtsH（丝状温度敏感蛋白酶H），一种参与膜蛋白降解的六聚体ATP酶，能够很容易地被改造以形成一维螺旋纳米管。FtsH纳米管需要持续的能量输入来维持其完整性，并随着ATP的伴随水解随时间降解，这类似于天然的依赖NTP的细胞骨架组装体。然而，与天然耗散系统不同的是，ATP水解由游离的FtsH原聚体催化，并且FtsH纳米管用于保存ATP，从而产生瞬态组装体，其寿命可通过在溶液中加入外部ATP酶从数天调节至数分钟。
