Staphylococcus pseudintermedius surface protein SpsD binds to extracellular matrix proteins to invade canine epithelial cells. Using single-molecule experiments, we show that SpsD engages in two modes of interaction with elastin that are tightly controlled by physical stress. Binding is weak (∼100 pN) at low tensile force (i.e. loading rate), but is dramatically enhanced (up to ∼1500 pN) by mechanical tension. Consistent with a “dock, lock, and latch” (DLL) mechanism, this force represents among the highest mechanical strengths known for a non-covalent biological interaction. The transition from weak to strong binding correlates with an increase in molecular stiffness but, surprisingly, with a decrease in molecular extension. This unanticipated mechanical behavior indicates that the adhesin is engaged in two distinct interaction mechanisms. Our results emphasize the crucial role of protein nanomechanics in the adhesion of staphylococci, and illustrate their wide diversity of force-dependent ligand-binding activities. These single-molecule mechanical experiments may contribute to the development of antiadhesion approaches to treat infections caused by S. pseudintermedius and other bacterial pathogens engaged in DLL interactions.

中文翻译：

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葡萄球菌粘附素SpsD和弹性蛋白之间分子复合物的纳米力学。

金黄色葡萄球菌表面蛋白SpsD与细胞外基质蛋白结合，侵袭犬上皮细胞。使用单分子实验，我们显示SpsD参与与弹性蛋白相互作用的两种模式，这两种模式都受到物理压力的严格控制。在低拉伸力下（即100 pN）结合力弱负载率），但由于机械张力而显着提高（高达1500 pN）。与“停靠，锁定和闩锁”（DLL）机制一致，此力代表了非共价生物相互作用所已知的最高机械强度。从弱结合到强结合的转变与分子刚度的增加有关，但是令人惊讶地与分子延伸的减少有关。这种出乎意料的机械行为表明，粘附素参与了两种不同的相互作用机制。我们的结果强调了蛋白质纳米力学在葡萄球菌粘附中的关键作用，并说明了其力依赖性配体结合活性的广泛多样性。这些单分子机械实验可能有助于开发抗粘连方法来治疗由细菌引起的感染假单胞菌和其他细菌病原体参与DLL相互作用。