Molecular Basis of the Dynamic Strength of the Sialyl Lewis X—Selectin Interaction

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.     

与Selectins相关的细胞粘附及有关疾病的药物研究

本文阐述了细胞粘附分子select in s 的作用机制以及由此引起的各种疾病, 综述了近几年来有关select in s 细胞粘附抑制剂的研究进展。     

PSGL-1——一种介导白细胞粘附的重要分子

PSGL-1是90年代初期发现的一种粘附分子，具有同源二聚体的结构，为一种跨膜的糖蛋白，表达于白细胞的表面，成熟PSGL-1分子上具有很多O-连接的糖基化位点，岩藻糖基化，唾液酸化和NH2末端酪氨酸的硫酸化对于PSGL-1的功能十分重要，PSGL-1是选择素P的配体，与选择素P具有特殊的亲和性，PSGL-1同时也是选择素L和选择素E的配体，PSGL-1与选择素分子的相互作用在白细胞粘附的起始阶段发挥着重要作用，PSGL-1在介导白细胞粘附的同时可以转导胞外信号，促进白细胞活化并使其稳定粘附，白细胞粘附具有重要的生理意义。