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Abstract：
Integrins are cell surface receptors crucial for cell migration and adhesion. They are activated by interactions of the talin head domain with the membrane surface and the integrin β cytoplasmic tail. Here, we use coarse-grained molecular dynamic simulations and nuclear magnetic resonance spectroscopy to elucidate the membrane-binding surfaces of the talin head (F2-F3) domain. In particular, we show that mutations in the four basic residues (K258E, K274E, R276E, and K280E) in the F2 binding surface reduce the affinity of the F2-F3 for the membrane and modify its orientation relative to the bilayer. Our results highlight the key role of anionic lipids in talin/membrane interactions. Simulation of the F2-F3 in complex with the α/β transmembrane dimer reveals information for its orientation relative to the membrane. Our studies suggest that the perturbed orientation of talin relative to the membrane in the F2 mutant would be expected to in turn perturb talin/integrin interactions.
摘要：
整合素是对细胞迁移和粘附至关重要的细胞表面受体。它们通过talin头结构域与膜表面和整联蛋白β细胞质尾的相互作用而被激活。这里,我们使用粗粒分子动力学模拟和核磁共振波谱来阐明距骨头部（F2-F3）域的膜结合表面。特别是,我们显示四个碱性残基(K258E，K274E,R276E,和F2结合表面中的K280E）降低了F2-F3对膜的亲和力，并改变了其相对于双层的取向。我们的结果强调了阴离子脂质在滑石/膜相互作用中的关键作用。与α/β跨膜二聚体复合的F2-F3的模拟揭示了其相对于膜的取向的信息。我们的研究表明，在F2突变体中，talin相对于膜的方向受到干扰，进而会干扰talin/整联蛋白的相互作用。
