Abstract：
Focal adhesions (FAs) are dynamic protein assemblies that connect cytoskeletons to the extracellular matrix and are crucial for cell adhesion and migration. KANKs are scaffold proteins that encircle FAs and act as key regulators of FA dynamics, but the molecular mechanism underlying their specified localization and functions remains poorly understood. Here, we determine the KANK1 structures in complex with talin and liprin-β, respectively. These structures, combined with our biochemical and cellular analyses, demonstrate how KANK1 scaffolds the FA core and associated proteins to modulate the FA shape in response to mechanical force. Additionally, we find that KANK1 undergoes liquid-liquid phase separation (LLPS), which is important for its localization at the FA edge and cytoskeleton connections to FAs. Our findings not only indicate the molecular basis of KANKs in bridging the core and periphery of FAs but also provide insights into the LLPS-mediated dynamic regulation of FA morphology.
摘要：
粘着斑（FAs）是将细胞骨架连接到细胞外基质的动态蛋白质组件，对于细胞粘附和迁移至关重要。KANK是包围FA的支架蛋白，并充当FA动力学的关键调节剂，但是它们特定的定位和功能的分子机制仍然知之甚少。这里,我们确定了与talin和liprin-β复合的KANK1结构，分别。这些结构，结合我们的生化和细胞分析，演示KANK1如何支撑FA核心和相关蛋白以响应机械力调节FA形状。此外,我们发现KANK1经历液-液相分离(LLPS)，这对于其在FA边缘的定位和与FA的细胞骨架连接是重要的。我们的发现不仅表明KANK在桥接FA的核心和外围方面的分子基础，而且还提供了对LLPS介导的FA形态动态调节的见解。
