Experimental Biophysics and Applied Nanoscience, Faculty of Physics, Bielefeld University, Bielefeld, Germany.
Biochemistry I, Faculty of Chemistry, Bielefeld University, Bielefeld, Germany.
Sci Rep. 2018 Nov 15;8(1):16849. doi: 10.1038/s41598-018-35120-0.
In non-covalent biological adhesion, molecular bonds commonly exhibit a monotonously decreasing life time when subjected to tensile forces (slip bonds). In contrast, catch bonds behave counter intuitively, as they show an increased life time within a certain force interval. To date only a hand full of catch bond displaying systems have been identified. In order to unveil their nature, a number of structural and phenomenological models have been introduced. Regardless of the individual causes for catch bond behavior, it appears evident that the free energy landscapes of these interactions bear more than one binding state. Here, we investigated the catch bond interaction between the hydrophilic domain of the human cell surface sulfatase 1 (Sulf1HD) and its physiological substrate heparan sulfate (HS) by atomic force microscopy based single molecule force spectroscopy (AFM-SMFS). Using Jarzynski's equality, we estimated the associated Gibbs free energy and provide a comprehensive thermodynamic and kinetic characterization of Sulf1HD/HS interaction. Interestingly, the binding potential landscape exhibits two distinct potential wells which confirms the recently suggested two state binding. Even though structural data of Sulf1HD is lacking, our results allow to draft a detailed picture of the directed and processive desulfation of HS.
在非共价生物黏附中，当分子键受到张力时（滑动键），通常表现出寿命单调递减的特性。相比之下，捕获键的行为则具有反直觉性，因为它们在一定的力区间内显示出寿命的增加。迄今为止，仅发现了少数几种具有捕获键特性的系统。为了揭示它们的本质，已经引入了许多结构和现象学模型。无论捕获键行为的具体原因是什么，很明显，这些相互作用的自由能景观具有不止一个结合状态。在这里，我们通过原子力显微镜基于单分子力谱（AFM-SMFS）研究了人类细胞表面磺基水解酶 1（Sulf1HD）的亲水结构域与其生理底物肝素硫酸盐（HS）之间的捕获键相互作用。利用 Jarzynski 等式，我们估计了相关的吉布斯自由能，并对 Sulf1HD/HS 相互作用进行了全面的热力学和动力学表征。有趣的是，结合势能景观表现出两个明显的势能阱，这证实了最近提出的两种状态结合。尽管缺乏 Sulf1HD 的结构数据，但我们的结果允许详细描绘 HS 的定向和连续脱硫过程。
