Cell Adhesion Laboratory, UF Scripps, Jupiter, FL, USA.
Department of Molecular Medicine, UF Scripps, Jupiter, FL, USA.
Nat Commun. 2024 Oct 28;15(1):9270. doi: 10.1038/s41467-024-52581-2.
Talin regulates crucial cellular functions, including cell adhesion and motility, and affects human diseases. Triggered by mechanical forces, talin plays crucial roles in facilitating the formation of focal adhesions and recruiting essential focal adhesion regulatory elements such as vinculin. The structural flexibility allows talin to fine-tune its signaling responses. This study presents our 2.7 Å cryoEM structures of talin, which surprisingly uncovers several auto-inhibitory states. Contrary to previous suggestions, our structures reveal that (1) the first and last three domains are not involved in maintaining talin in its closed state and are mobile, (2) the talin F-actin and membrane binding domain are loosely attached and thus available for binding, and (3) the main force-sensing domain is oriented with its vinculin binding sites ready for release. These structural snapshots offer insights and advancements in understanding the dynamic talin activation mechanism, which is crucial for mediating cell adhesion.
塔林调节关键的细胞功能，包括细胞黏附和运动，并影响人类疾病。塔林在机械力的触发下，在促进黏附斑形成和招募必需的黏附斑调节元件（如 vinculin）方面发挥关键作用。结构的灵活性使塔林能够微调其信号响应。本研究展示了我们的 2.7 Å 冷冻电镜结构，令人惊讶的是，这些结构揭示了几个自动抑制状态。与之前的建议相反，我们的结构表明：（1）第一和最后三个结构域不参与将塔林保持在其关闭状态，而是可移动的；（2）塔林与肌动蛋白和膜结合的结构域是松散连接的，因此可用于结合；（3）主要的力感应结构域被定向，其 vinculin 结合位点准备释放。这些结构快照为理解动态塔林激活机制提供了新的见解和进展，该机制对于介导细胞黏附至关重要。
