Molecular basis of the dynamic strength of the sialyl Lewis X--selectin interaction.
Molecular basis of the dynamic strength of the sialyl Lewis X--selectin interaction.
复制标题
唾液酸路易斯 X-选择素相互作用的动态强度的分子基础。
DOI：
10.1002/cphc.200300813
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Moy,VincentT
中科院分区：
文献类型：
--
作者：
Zhang,Xiaohui;Bogorin,DanielaF;Moy,VincentT
选择素是Ca 2+依赖性细胞粘附分子，通过结合碳水化合物部分促进白细胞与血管内皮的初始附着，如四糖，唾液酸刘易斯X（sLeX）。选择素-sLeX相互作用的一个重要特性是它能够承受血流的流体动力。在本文中，我们使用单分子动态力光谱（DFS）来鉴定sLeX内引起选择素/sLeX相互作用的动态性质的分子决定簇。我们的原子力显微镜（AFM）测量显示，选择素/sLeX复合物的解结合涉及克服至少两个激活障碍。内屏障，这决定了在高的力的复合物的动态响应，是由之间的相互作用的Fuc残基sLeX和螯合到选择素分子的凝集素结构域的Ca 2+离子，而外部激活屏障可以归因于涉及sLeX的唾液酸残基的相互作用。由于其陡峭的内部激活屏障，选择素-sLeX复合物对高拉力不太敏感。因此，除了对键能的贡献外，Ca 2+离子还赠款选择素-sLeX复合物拉伸强度，这对于选择素介导的白细胞滚动至关重要。
The selectins are Ca2+‐dependent cell adhesion molecules that facilitate the initial attachment of leukocytes to the vascular endothelium by binding to a carbohydrate moiety as exemplified by the tetrasaccharide, sialyl Lewis X (sLeX). An important property of the selectin‐sLeX interaction is its ability to withstand the hydrodynamic force of the blood flow. Herein, we used single‐molecule dynamic force spectroscopy (DFS) to identify the molecular determinants within sLeX that give rise to the dynamic properties of the selectin/sLeX interaction. Our atomic force microscopy (AFM) measurements revealed that the unbinding of the selectin/sLeX complexes involves overcoming at least two activation barriers. The inner barrier, which determines the dynamic response of the complex at high forces, is governed by the interaction between the Fuc residue of sLeX and a Ca2+ion chelated to the lectin domain of the selectin molecule, whereas the outer activation barrier can be attributed to interactions involving the sialic acid residue of sLeX. Due to their steep inner activation barriers, the selectin‐sLeX complexes are less sensitive to high pulling forces. Hence, besides its contribution to the bond energy, the Ca2+ion also grants the selectin–sLeX complexes a tensile strength that is crucial for the selectin‐mediated rolling of leukocytes.