Abstract：
Phagocytosis is an essential mechanism of the human immune system where pathogens are eliminated by immune cells. The CCN1 protein plays an important role in the phagocytosis of Staphylococcus aureus by favoring the bridging of the αVβ3 integrin to the bacterial peptidoglycan (PG), through mechanical forces that remain unknown. Here, we employ single-molecule experiments to unravel the nanomechanics of the PG-CCN1-αVβ3 ternary complex. While CCN1 binds αVβ3 integrins with moderate force (∼60 pN), much higher binding strengths (up to ∼800 pN) are observed between CCN1 and PG. Notably, the strength of both CCN1-αVβ3 and CCN1-PG bonds is dramatically enhanced by tensile loading, favoring a model in which mechanical stress induces the exposure of cryptic integrin binding sites in CCN1 and multivalent binding between CCN1 lectin sites and monosaccharides along the PG glycan chains.
摘要：
吞噬作用是人体免疫系统的基本机制，其中病原体被免疫细胞消除。CCN1蛋白通过促进αVβ3整联蛋白与细菌肽聚糖（PG）的桥接，在金黄色葡萄球菌的吞噬作用中起着重要作用，通过未知的机械力。这里,我们采用单分子实验来解开PG-CCN1-αVβ3三元复合物的纳米力学。当CCN1以中等的力(~60pN)结合αVβ3整合素时，在CCN1和PG之间观察到更高的结合强度(高达800pN)。值得注意的是,CCN1-αVβ3和CCN1-PG键的强度通过拉伸载荷显着增强，有利于机械应力诱导CCN1中隐蔽整合素结合位点的暴露以及CCN1凝集素位点与PG聚糖链单糖之间的多价结合的模型。
