Department of Physics, Syracuse University, 201 Physics Building, Syracuse, New York 13244-1130, United States.
Ichor Life Sciences, Inc., 2651 US Route 11, LaFayette, New York 13084, United States.
J Phys Chem Lett. 2022 May 12;13(18):4021-4028. doi: 10.1021/acs.jpclett.2c00621. Epub 2022 Apr 29.
Surface-tethered ligand-receptor complexes are key components in biological signaling and adhesion. They also find increasing utility in single-molecule assays and biotechnological applications. Here, we study the real-time binding kinetics between various surface-immobilized peptide ligands and their unrestrained receptors. A long peptide tether increases the association of ligand-receptor complexes, experimentally proving the fly casting mechanism where the disorder accelerates protein recognition. On the other hand, a short peptide tether enhances the complex dissociation. Notably, the rate constants measured for the same receptor, but under different spatial constraints, are strongly correlated to one another. Furthermore, this correlation can be used to predict how surface tethering on a ligand-receptor complex alters its binding kinetics. Our results have immediate implications in the broad areas of biomolecular recognition, intrinsically disordered proteins, and biosensor technology.
表面束缚的配体-受体复合物是生物信号转导和黏附中的关键组成部分。它们在单分子检测和生物技术应用中也得到了越来越多的应用。在这里，我们研究了各种表面固定化肽配体与其无约束受体之间的实时结合动力学。长肽连接物增加了配体-受体复合物的缔合，从实验上证明了无序加速蛋白质识别的飞钓机制。另一方面，短肽连接物增强了复合物的解离。值得注意的是，在不同空间限制下测量的同一受体的速率常数彼此之间具有强烈的相关性。此外，这种相关性可用于预测配体-受体复合物表面束缚如何改变其结合动力学。我们的研究结果在生物分子识别、无规卷曲蛋白质和生物传感器技术等广泛领域具有直接的意义。
