PDF(Pubmed)
Abstract：
Regulation of the assembly and turnover of branched actin filament networks nucleated by the Arp2/3 complex is essential during many cellular processes, including cell migration and membrane trafficking. Cortactin is important for actin branch stabilization, but the mechanism by which this occurs is unclear. Given this, we determined the structure of vertebrate cortactin-stabilized Arp2/3 actin branches using cryogenic electron microscopy. We find that cortactin interacts with the new daughter filament nucleated by the Arp2/3 complex at the branch site, rather than the initial mother actin filament. Cortactin preferentially binds activated Arp3. It also stabilizes the F-actin-like interface of activated Arp3 with the first actin subunit of the new filament, and its central repeats extend along successive daughter-filament subunits. The preference of cortactin for activated Arp3 explains its retention at the actin branch and accounts for its synergy with other nucleation-promoting factors in regulating branched actin network dynamics.
摘要：
在许多细胞过程中，调节由Arp2/3复合物成核的支链肌动蛋白丝网络的组装和周转是必不可少的，包括细胞迁移和膜运输。肌动蛋白对肌动蛋白分支稳定很重要，但这种情况发生的机制尚不清楚。鉴于此,我们使用低温电子显微镜确定了脊椎动物cortactin稳定的Arp2/3肌动蛋白分支的结构。我们发现cortactin在分支位点与由Arp2/3复合物成核的新子丝相互作用，而不是最初的母体肌动蛋白丝。Cortactin优先结合活化的Arp3。它还稳定了激活的Arp3与新丝的第一个肌动蛋白亚基的F-肌动蛋白样界面，及其中心重复序列沿连续的子纤丝亚基延伸。cortactin对活化的Arp3的偏好解释了其在肌动蛋白分支的保留，并解释了其与其他成核促进因子在调节分支肌动蛋白网络动力学中的协同作用。
