Department of Chemistry, University of Rochester, Rochester, New York, USA.
Biophys J. 2011 Oct 19;101(8):2026-36. doi: 10.1016/j.bpj.2011.09.005.
Catch-binding is a counterintuitive phenomenon in which the lifetime of a receptor/ligand bond increases when a force is applied to break the bond. Several mechanisms have been proposed to rationalize catch-binding. In the two-pathway model, the force drives the system away from its native dissociation pathway into an alternative pathway involving a higher energy barrier. Here, we analyze an allosteric model suggesting that a force applied to the complex alters the distribution of receptor conformations, and as a result, induces changes in the ligand-binding site. The model assumes explicitly that the allosteric transitions govern the properties of the ligand site. We demonstrate that the dynamics of the ligand is described by two relaxation times, one of which arises from the allosteric site. Therefore, we argue that one can characterize the allosteric transitions by studying the receptor/ligand binding. We show that the allosteric description reduces to the two-pathway model in the limit when the allosteric transitions are faster than the bond dissociation. The formal results are illustrated with two systems, P-selectin/PSGL-1 and FimH/mannose, subjected to both constant and time-dependent forces. The report advances our understanding of catch-binding by combining alternative physical models into a unified description and makes the problem more tractable for the bond mechanics community.
捕获结合是一种反直觉的现象，即在打破键时施加力会增加受体/配体键的寿命。已经提出了几种机制来合理化捕获结合。在双通道模型中，力将系统从其天然解离途径驱动到涉及更高能垒的替代途径。在这里，我们分析了一个变构模型，该模型表明施加到复合物上的力改变了受体构象的分布，从而导致配体结合位点发生变化。该模型明确假设变构跃迁控制配体位点的性质。我们证明，配体的动力学由两个弛豫时间描述，其中一个来自变构位点。因此，我们认为可以通过研究受体/配体结合来表征变构跃迁。我们表明，当变构跃迁比键离解快时，变构描述简化为双通道模型。正式的结果用两个系统进行了说明，即 P-选择素/PSGL-1 和 FimH/甘露糖，它们受到恒力和时变力的作用。该报告通过将替代物理模型结合到统一描述中，加深了我们对捕获结合的理解，并使该问题对键力学社区更具可操作性。
