研究人员展示了由三种不同的formin结合的肌动蛋白丝（F-actin）带刺末端的高分辨率冷冻电镜结构，揭示了由丝状物施加的共同不对称formin构象。在肌动蛋白聚合过程中形成的新的亚基间接触会使formin发生立体位移并引发其移位。
这种“解锁-锁定”机制解释了肌动蛋白-丝的生长如何与formin的运动相协调。丝的伸长速度由肌动蛋白-formin界面的定位和稳定性控制，而formin界面可区分快和慢formin。此外，研究人员还提供了肌动蛋白-formin-抑制蛋白环复合物的结构，该结构解析了丝伸长过程中抑制蛋白如何从倒钩末端快速释放。
据悉，在真核生物中，formin控制着驱动细胞形态发生和运动的F-actin的组装。然而，它们与F-actin的分子相互作用及其作用机制仍不清楚。
附：英文原文
Title: Molecular mechanism of actin filament elongation by formins
Author: Wout Oosterheert, Micaela Boiero Sanders, Johanna Funk, Daniel Prumbaum, Stefan Raunser, Peter Bieling
Issue&Volume: 2024-04-12
Abstract: Formins control the assembly of actin filaments (F-actin) that drive cell morphogenesis and motility in eukaryotes. However, their molecular interaction with F-actin and their mechanism of action remain unclear. In this work, we present high-resolution cryo–electron microscopy structures of F-actin barbed ends bound by three distinct formins, revealing a common asymmetric formin conformation imposed by the filament. Formation of new intersubunit contacts during actin polymerization sterically displaces formin and triggers its translocation. This “undock-and-lock” mechanism explains how actin-filament growth is coordinated with formin movement. Filament elongation speeds are controlled by the positioning and stability of actin-formin interfaces, which distinguish fast and slow formins. Furthermore, we provide a structure of the actin-formin-profilin ring complex, which resolves how profilin is rapidly released from the barbed end during filament elongation.
DOI: adn9560
Source: https://www.science.org/doi/10.1126/science.adn9560