Formins play crucial roles in actin polymerization by nucleating filaments and regulating their elongation. Formins bind the barbed ends of filaments via their dimeric FH2 domains, which step processively onto incoming actin subunits during elongation. Actin monomers can bind formin-bound barbed ends directly or undergo diffusion-mediated delivery through interactions with formin FH1 domains and profilin. Despite its fundamental importance, a clear mechanism governing processive FH2 stepping has remained elusive. In this study, we systematically characterized the polymerization behavior of the S. cerevisiae formin Bni1p using in vitro reconstitution assays and stochastic simulations. We found that Bni1p assembles populations of filaments with lengths that depend nonlinearly on the rate of elongation. This processive behavior is dictated by a variable probability of dissociation that depends on the reaction conditions. Bni1p dissociates from barbed ends with a basal off-rate, which enables prolonged filament assembly over the course of a long lifetime at the barbed end. A bias towards FH1-mediated delivery as the dominant mechanism for polymerization curtails elongation by shortening the lifetime of the formin at the filament end. This facilitates the assembly of populations of filaments with similar average lengths, even when polymerization proceeds at different rates. Our results suggest a central role for formin FH1 domains in regulating processivity. The specific effects of FH1 domains on processivity are variable and likely tailored to the physiological function of each formin.

中文翻译：

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亚基添加模式调节福尔马币对肌动蛋白丝的进行性伸长。


福尔马辛通过成核细丝并调节其伸长率在肌动蛋白聚合中起关键作用。福尔曼蛋白通过其二聚体 FH2 结构域结合细丝的倒钩末端，这些结构域在伸长过程中进行性地步入进入的肌动蛋白亚基。肌动蛋白单体可以直接结合福尔辛结合的倒钩末端，或通过与福尔金 FH1 结构域和 profilin 相互作用进行扩散介导的递送。尽管 FH2 进行性步进具有根本性的重要性，但控制 FH2 步进的明确机制仍然难以捉摸。在这项研究中，我们使用体外重构测定和随机模拟系统地表征了酿酒酵母福菌素 Bni1p 的聚合行为。我们发现 Bni1p 组装了长度非线性取决于伸长率的细丝群。这种进行过程中的行为由可变的解离概率决定，该概率取决于反应条件。Bni1p 以基底脱落速率从倒钩端解离，这使得在倒钩端的长寿命过程中能够延长细丝组装时间。偏向于 FH1 介导的递送作为聚合的主要机制，通过缩短福尔辛在细丝末端的寿命来减少伸长率。这有助于组装具有相似平均长度的细丝群，即使聚合以不同的速率进行时也是如此。我们的结果表明福尔金 FH1 结构域在调节持续合成能力中起着核心作用。FH1 结构域对持续合成能力的特定影响是可变的，并且可能根据每种福尔马辛的生理功能量身定制。