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.

中文翻译：

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福尔明延长肌动蛋白丝的分子机制


福尔明控制肌动蛋白丝 (F-肌动蛋白) 的组装，从而驱动真核生物中的细胞形态发生和运动。然而，它们与 F-肌动蛋白的分子相互作用及其作用机制仍不清楚。在这项工作中，我们展示了由三种不同的福明结合的F-肌动蛋白带刺末端的高分辨率冷冻电子显微镜结构，揭示了由细丝施加的常见不对称福明构象。肌动蛋白聚合过程中新的亚基间接触的形成会在空间上取代福尔明并触发其易位。这种“脱离和锁定”机制解释了肌动蛋白丝的生长如何与福明运动协调。丝的伸长速度由肌动蛋白-形成蛋白界面的定位和稳定性控制，该界面区分快和慢的形成蛋白。此外，我们提供了肌动蛋白-形成蛋白-profilin环复合物的结构，该结构解决了肌动蛋白在丝伸长过程中如何从有刺末端快速释放的问题。