Viela Felipe, Speziale Pietro, Pietrocola Giampiero, Dufrêne Yves F
Institute of Life Sciences, Université catholique de Louvain, Croix du Sud, 4-5, bte L7.07.06, B-1348 Louvain-la-Neuve, Belgium.
Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, Viale Taramelli 3/b, 27100 Pavia, Italy.
Microb Cell. 2019 Jun 11;6(7):321-323. doi: 10.15698/mic2019.07.684.
Attachment of to platelets and endothelial cells involves binding of bacterial cell surface protein A (SpA) to the large plasma glycoprotein von Willebrand factor (vWF). SpA-mediated bacterial adhesion to vWF is controlled by fluid shear stress, yet little is currently known about the underlying molecular mechanism. In a recent publication, we showed that the SpA-vWF interaction is tightly regulated by mechanical force. By means of single-molecule pulling experiments, we found that the SpA-vWF bond is extremely strong, being able to resist forces which largely outperform the strength of typical receptor-ligand bonds. In line with flow experiments, strong adhesion is activated by mechanical tension. These results suggest that force induces conformational changes in the vWF molecule, from a globular to an extended state, leading to the exposure of cryptic binding sites to which SpA strongly binds. This force-sensitive mechanism may largely contribute to help bacteria to resist shear stress of flowing blood during infection.
[细菌名称]与血小板和内皮细胞的附着涉及细菌细胞表面蛋白A（SpA）与血浆大糖蛋白血管性血友病因子（vWF）的结合。SpA介导的细菌与vWF的粘附受流体剪切应力控制，但目前对其潜在分子机制知之甚少。在最近的一篇出版物中，我们表明SpA-vWF相互作用受到机械力的严格调节。通过单分子拉伸实验，我们发现SpA-vWF键极其牢固，能够抵抗大大超过典型受体-配体键强度的力。与流动实验一致，强粘附通过机械张力激活。这些结果表明，力诱导vWF分子构象从球状变为伸展状态，导致隐蔽结合位点暴露，SpA与之强烈结合。这种力敏感机制可能在很大程度上有助于[细菌名称]在感染期间抵抗流动血液的剪切应力。
