Wang J H, Smolyar A, Tan K, Liu J H, Kim M, Sun Z Y, Wagner G, Reinherz E L
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Cell. 1999 Jun 11;97(6):791-803. doi: 10.1016/s0092-8674(00)80790-4.
Interaction between CD2 and its counterreceptor, CD58 (LFA-3), on opposing cells optimizes immune recognition, facilitating contacts between helper T lymphocytes and antigen-presenting cells as well as between cytolytic effectors and target cells. Here, we report the crystal structure of the heterophilic adhesion complex between the amino-terminal domains of human CD2 and CD58. A strikingly asymmetric, orthogonal, face-to-face interaction involving the major beta sheets of the respective immunoglobulin-like domains with poor shape complementarity is revealed. In the virtual absence of hydrophobic forces, interdigitating charged amino acid side chains form hydrogen bonds and salt links at the interface (approximately 1200 A2), imparting a high degree of specificity albeit with low affinity (K(D) of approximately microM). These features explain CD2-CD58 dynamic binding, offering insights into interactions of related immunoglobulin superfamily receptors.
CD2与其在相对细胞上的反受体CD58（淋巴细胞功能相关抗原3，LFA-3）之间的相互作用优化了免疫识别，促进辅助性T淋巴细胞与抗原呈递细胞之间以及溶细胞效应细胞与靶细胞之间的接触。在此，我们报道了人CD2和CD58氨基末端结构域之间异嗜性粘附复合物的晶体结构。结果显示，一种涉及各自免疫球蛋白样结构域主要β折叠的显著不对称、正交、面对面相互作用，其形状互补性较差。在几乎不存在疏水作用力的情况下，相互交叉的带电荷氨基酸侧链在界面处（约1200 Ų）形成氢键和盐键，赋予了高度特异性，尽管亲和力较低（解离常数K(D)约为微摩尔级别）。这些特征解释了CD2 - CD58的动态结合，为相关免疫球蛋白超家族受体的相互作用提供了见解。
