Integrin receptors regulate normal cellular processes such as signaling, cell migration, adhesion to the extracellular matrix, and leukocyte function. Talin recruitment to the membrane is necessary for its binding to and activation of integrin. Vertebrates have two highly conserved talin homologs that differ in their expression patterns. The F1–F3 FERM subdomains of cytoskeletal proteins resemble a cloverleaf, but in talin1, its F1 subdomain and additional F0 subdomain align more linearly with its F2 and F3 subdomains. Here, we present the talin2 crystal structure, revealing that its F0-F1 di-subdomain displays another unprecedented constellation, whereby the F0-F1-F2 adopts a new cloverleaf-like arrangement. Using multiangle light scattering (MALS), fluorescence lifetime imaging (FLIM), and FRET analyses, we found that substituting the corresponding residues in talin2 that abolish lipid binding in talin1 disrupt the binding of talin to the membrane, focal adhesion formation, and cell spreading. Our results provide the molecular details of the functions of specific talin isoforms in cell adhesion.

中文翻译：

---

独特的 talin2 结构指导细胞粘附中的异构体特异性。

整联蛋白受体调节正常的细胞过程，例如信号传导、细胞迁移、与细胞外基质的粘附和白细胞功能。Talin 募集到膜是其结合和激活整联蛋白所必需的。脊椎动物有两个高度保守的 talin 同源物，它们的表达模式不同。细胞骨架蛋白的 F1-F3 FERM 子域类似于三叶草，但在 talin1 中，其 F1 子域和额外的 F0 子域与其 F2 和 F3 子域更线性地对齐。在这里，我们展示了 talin2 晶体结构，揭示了它的 F0-F1 双子域显示了另一个前所未有的星座，即 F0-F1-F2 采用了一种新的三叶草状排列。使用多角度光散射 (MALS)、荧光寿命成像 (FLIM) 和 FRET 分析，我们发现替换 talin2 中相应的残基会破坏 talin1 中的脂质结合，从而破坏了 talin 与膜的结合、粘着斑形成和细胞扩散。我们的结果提供了特定 talin 亚型在细胞粘附中的功能的分子细节。