Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48.
Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48.
复制标题
直接测量细胞表面蛋白 CD2 和 CD48 之间的异型粘附。
DOI：
10.1021/bi020296g
复制
发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
Leckband,DeborahE
中科院分区：
文献类型：
--
作者：
Zhu,Boru;Davies,ElizabethA;vanderMerwe,PAnton;Calvert,Tammy;Leckband,DeborahE
直接力测量被用来研究小鼠T细胞粘附糖蛋白CD 2和其配体CD 48之间的嗜异性粘附的分子机制。从蛋白质-蛋白质相互作用势的距离依赖性，我们直接证明了全长胞外结构域以头对头方向粘附。蛋白质之间不存在长程静电吸引，这进一步表明结合表面之间的盐桥只影响短程相互作用。尽管在CD 2的结构域1（D1）中失去了稳定的二硫键，但粘附失败突然发生，没有证据表明在分离期间部分蛋白质解折叠。最后，这些延伸的膜表面之间的测量直接证实了低亲和力的CD 2 − CD 48键产生弱粘附，并且侧向受体迁移是形成可观粘附所必需的。这是第一次直接测量的范围和规模的部队管理异型粘附介导的细胞表面蛋白。这些结果既验证了头对头CD 2 − CD 48对接比对，也证明了从测量的相互作用势的距离依赖性阐明粘附蛋白的结构-功能关系的能力。
Direct force measurements were used to investigate the molecular mechanism of heterophilic adhesion between the murine T-cell adhesion glycoprotein CD2 and its ligand CD48. From the distance dependence of the protein−protein interaction potential, we demonstrate directly that the full-length extracellular domains adhere in a head-to-head orientation. The absence of long-range electrostatic protein−protein attraction further indicates that the salt bridges between the binding surfaces only influence the interaction at short range. Despite the loss of a stabilizing disulfide bond in domain 1 (D1) of CD2, adhesive failure occurs abruptly with no evidence of partial protein unfolding during detachment. Finally, these measurements between extended membrane surfaces directly confirm that the low-affinity CD2−CD48 bond generates weak adhesion and that lateral receptor mobility is required for the development of appreciable adhesion. This is the first direct measurement of the range and magnitude of the forces governing heterotypic adhesion mediated by cell surface proteins. These results both verified the head-to-head CD2−CD48 docking alignment and demonstrated the ability to elucidate the structure−function relationships of adhesion proteins from the measured distance dependence of their interaction potentials.