Wang J, Springer T A
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachussetts, USA.
Immunol Rev. 1998 Jun;163:197-215. doi: 10.1111/j.1600-065x.1998.tb01198.x.
The circulation and migration of leukocytes are critical for immune surveillance and immune response to infection or injury. The key step of leukocyte recruitment involves the adhesion between immunoglobulin superfamily (IgSF) proteins on endothelium and integrin molecules on leukocyte surfaces. Some of the IgSF members are subverted as virus receptors. Four crystal structures of N-terminal two-domain fragments of these IgSF proteins have been determined: intercellular adhesion molecule-1 (ICAM-1), ICAM-2, vascular adhesion molecule-1 (VCAM-1), and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). An acidic residue near the bottom of domain 1 plays a key role in integrin binding. For ICAM-1 and ICAM-2, this glutamic acid residue is located on a flat surface, complementary to the flat surface of the I domain of the integrin to which they bind, lymphocyte function-associated antigen-1 (LFA-1). For VCAM-1 and MAdCAM-1, the acidic residue is aspartic acid, and it resides on a protruded CD loop which may be complementary to a more pocket-like structure in the alpha 4 integrins to which they bind, which lack I domains. A number of unique structural features of this subclass of IgSF have been identified which are proposed to consolidate the domain structure to resist force during adhesion to integrins. Different mechanisms are proposed for the different CAMs to present the integrin-binding surface toward the opposing cell for adhesion, and prevent cis interaction with integrins on the same cell. Finally, CD4 and ICAM-1 are compared in the context of ligand binding and virus binding, which shows how human immunodeficiency virus and rhinovirus fit well with the distinct structural feature of their cognate receptors.
白细胞的循环和迁移对于免疫监视以及对感染或损伤的免疫反应至关重要。白细胞募集的关键步骤涉及内皮细胞上免疫球蛋白超家族（IgSF）蛋白与白细胞表面整合素分子之间的黏附。一些IgSF成员被用作病毒受体。已经确定了这些IgSF蛋白的N端两个结构域片段的四种晶体结构：细胞间黏附分子-1（ICAM-1）、ICAM-2、血管细胞黏附分子-1（VCAM-1）和黏膜地址素细胞黏附分子-1（MAdCAM-1）。结构域1底部附近的一个酸性残基在整合素结合中起关键作用。对于ICAM-1和ICAM-2，这个谷氨酸残基位于一个平面上，与它们所结合的整合素I结构域的平面互补，即淋巴细胞功能相关抗原-1（LFA-1）。对于VCAM-1和MAdCAM-1，酸性残基是天冬氨酸，它位于一个突出的CD环上，该环可能与它们所结合的α4整合素中更像口袋的结构互补，这些α4整合素缺乏I结构域。已经确定了IgSF这一亚类的许多独特结构特征，这些特征被认为可以巩固结构域结构，以在与整合素黏附时抵抗外力。对于不同的细胞黏附分子（CAM），提出了不同的机制，使整合素结合表面朝向相对的细胞以进行黏附，并防止与同一细胞上的整合素发生顺式相互作用。最后，在配体结合和病毒结合的背景下对CD4和ICAM-1进行了比较，这显示了人类免疫缺陷病毒和鼻病毒如何与其同源受体的独特结构特征相契合。
