The adhesin FimH is expressed by commensal Escherichia coli and is implicated in urinary tract infections, where it mediates adhesion to mannosylated glycoproteins on urinary and intestinal epithelial cells in the presence of a high-shear fluid environment. The FimH-mannose bond exhibits catch behavior in which bond lifetime increases with force, because tensile force induces a transition in FimH from a compact native to an elongated activated conformation with a higher affinity to mannose. However, the lifetime of the activated state of FimH has not been measured under force. Here we apply multiplexed magnetic tweezers to apply a preload force to activate FimH bonds with yeast mannan, then we measure the lifetime of these activated bonds under a wide range of forces above and below the preload force. A higher fraction of FimH-mannan bonds were activated above than below a critical preload force, confirming the FimH catch bond behavior. Once activated, FimH detached from mannose with multi-state kinetics, suggesting the existence of two bound states with a 20-fold difference in dissociation rates. The average lifetime of activated FimH-mannose bonds was 1000 to 10,000 s at forces of 30–70 pN. Structural explanations of the two bound states and the high force resistance provide insights into structural mechanisms for long-lived, force-resistant biomolecular interactions.

中文翻译：

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FimH-甘露糖非共价键在压力下可存活几分钟到几小时


粘附素 FimH 由共生大肠杆菌表达，与尿路感染有关，在高剪切流体环境下，它介导尿路和肠上皮细胞上甘露糖化糖蛋白的粘附。 FimH-甘露糖键表现出捕获行为，其中键寿命随着力的增加而增加，因为张力诱导 FimH 从紧凑的天然构象转变为对甘露糖具有更高亲和力的细长活化构象。然而，FimH 激活状态的寿命尚未在力下测量。在这里，我们使用多重磁性镊子施加预紧力来激活与酵母甘露聚糖的 FimH 键，然后我们测量这些激活的键在预紧力之上和之下的各种力下的寿命。高于临界预紧力时，较高比例的 FimH-甘露聚糖键被激活，这证实了 FimH 捕获键行为。一旦激活，FimH 就会以多态动力学与甘露糖分离，这表明存在两种解离速率相差 20 倍的结合态。在 30-70 pN 的力下，活化的 FimH-甘露糖键的平均寿命为 1000 至 10,000 秒。对两种束缚态和高抗力的结构解释提供了对长寿命、抗力生物分子相互作用的结构机制的见解。