Department of Chemical Engineering, Texas A&M University, 3122 TAMU, College Station, TX USA.
Glycobiology. 2019 May 1;29(5):397-408. doi: 10.1093/glycob/cwz010.
We recently discovered that the nature of lectin multivalency and glycolipid diffusion on cell membranes could lead to the heteromultivalent binding (i.e., a single lectin simultaneously binding to different types of glycolipid ligands). This heteromultivalent binding may even govern the lectin-glycan recognition process. To investigate this, we developed a kinetic Monte Carlo simulation, which only considers the fundamental physics/chemistry principles, to model the process of lectin binding to glycans on cell surfaces. We found that the high-affinity glycan ligands could facilitate lectin binding to other low-affinity glycan ligands, even though these low-affinity ligands are barely detectable in microarrays with immobilized glycan ligands. Such heteromultivalent binding processes significantly change lectin binding behaviors. We hypothesize that living organisms probably utilize this mechanism to regulate the downstream lectin functions. Our finding not only offers a mechanism to describe the concept that lectins are pattern recognition molecules, but also suggests that the two overlooked parameters, surface diffusion of glycan ligand and lectin binding kinetics, can play important roles in glycobiology processes. In this paper, we identified the critical parameters that influence the heteromultivalent binding process. We also discussed how our discovery can impact the current lectin-glycan analysis.
我们最近发现，凝集素的多价性和糖脂在细胞膜上的扩散性质可能导致异多价结合（即，单个凝集素同时结合不同类型的糖脂配体）。这种异多价结合甚至可能控制凝集素-糖识别过程。为了研究这一点，我们开发了一种仅考虑基本物理/化学原理的动力学蒙特卡罗模拟，以模拟凝集素与细胞表面糖链的结合过程。我们发现，高亲和力糖配体可以促进凝集素与其他低亲和力糖配体的结合，即使这些低亲和力配体在固定糖配体的微阵列中几乎无法检测到。这种异多价结合过程显著改变了凝集素的结合行为。我们假设，生物可能利用这种机制来调节下游的凝集素功能。我们的发现不仅提供了一种机制来描述凝集素是模式识别分子的概念，还表明两个被忽视的参数，即糖配体的表面扩散和凝集素结合动力学，在糖生物学过程中可以发挥重要作用。在本文中，我们确定了影响异多价结合过程的关键参数。我们还讨论了我们的发现如何影响当前的凝集素-糖分析。
