Low affinity interaction of human or rat T cell adhesion molecule CD2 with its ligand aligns adhering membranes to achieve high physiological affinity
Low affinity interaction of human or rat T cell adhesion molecule CD2 with its ligand aligns adhering membranes to achieve high physiological affinity
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DOI：
10.1074/jbc.272.49.30889
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发表时间：
1997-12-05
影响因子：
4.8
通讯作者：
van der Merwe, PA
中科院分区：
文献类型：
--
作者：
Dustin, ML;Golan, DE;van der Merwe, PA
低亲和力粘附分子产生稳定细胞粘附的机制尚不清楚。在溶液中，人CD2与其配体CD58的相互作用具有低亲和力（500 mM(-1)），大鼠CD2与其配体CD48的相互作用具有更低亲和力（40 mM(-1)）。然而，在分子水平上，这两个系统在拓扑结构上可能是相同的。制备了荧光标记的糖基磷脂酰肌醇锚定的CD48和CD58，并将其掺入支撑的磷脂双分子层中，其中配体能够自由横向扩散，定量荧光成像研究了Jurkat细胞与双分子层接触区域人类和大鼠CD2分子与荧光配体的结合。这些研究提供了两个主要结论。首先，CD2/配体相互作用以纳米精度排列膜，导致生理上有效的二维亲和力。这个过程不需要CD2完整的细胞质尾部。其次，拓扑学上相似的受体可以实现的膜对齐程度随着亲和力的降低而恶化。这表明这种协同模式实现稳定的细胞-细胞粘附的能力的亲和力限制在大约10 mM（-1）。
The mechanism by which low affinity adhesion molecules function to produce stable cell-cell adhesion is unknown. In solution, the interaction of human CD2 with its ligand CD58 is of low affinity (500 mM(-1)) and the interaction of rat CD2 with its ligand CD48 is of still lower affinity (40 mM(-1)). At the molecular level, however, the two systems are likely to be topologically identical. Fluorescently labeled glycosylphosphatidylinositol-anchored CD48 and CD58 were prepared and incorporated into supported phospholipid bilayers, in which the ligands were capable of free lateral diffusion, Quantitative fluorescence imaging was used to study the binding of cell surface human and rat CD2 molecules to the fluorescent ligands in contact areas between Jurkat cells and the bilayers. These studies provide two major conclusions. First, CD2/ligand interactions cooperate to align membranes with nanometer precision leading to a physiologically effective two-dimensional affinity. This process does not require the intact cytoplasmic tail of CD2. Second, the degree of membrane alignment that can be achieved by topologically similar receptors deteriorates with decreasing affinity. This suggests an affinity limit for the ability of this mode of cooperativity to achieve stable cell-cell adhesion at approximately 10 mM(-1).