Holness C L, Bates P A, Little A J, Buckley C D, McDowall A, Bossy D, Hogg N, Simmons D L
Cell Adhesion Laboratory, John Radcliffe Hospital, Headington, Oxford, London, United Kingdom.
J Biol Chem. 1995 Jan 13;270(2):877-84. doi: 10.1074/jbc.270.2.877.
Intercellular adhesion molecule 3 (ICAM-3, CD50) is a member of the immunoglobulin superfamily and is a constitutively expressed ligand for the leukocyte integrin LFA-1 (CD11a/CD18). ICAM-3 is expressed at high levels by all resting leukocyte populations and antigen presenting cells and is a major ligand for LFA-1 in the resting immune system. ICAM-3 is a signal transducer and may play a key role in initiating immune responses. Mutant ICAM-3 Fc-chimeric proteins were quantitatively analyzed for their ability to bind COS cells expressing human LFA-1. The LFA-1-binding site on ICAM-3 is located in the N-terminal 2 Ig domains. Domains 3-5 do not significantly contribute to adhesion. The binding site has been further resolved by rational targeting of 14 point mutations throughout domains 1 and 2, coupled with modeling studies. Within domain 1 a cluster of residues (Glu37, Leu66, Ser68, and Gln75), that are predicted to lie on the CC'FG face of the Ig fold, play a dominant role in LFA-1 binding.
细胞间黏附分子3（ICAM - 3，CD50）是免疫球蛋白超家族的成员，是白细胞整合素LFA - 1（CD11a/CD18）的组成性表达配体。ICAM - 3在所有静息白细胞群体和抗原呈递细胞中高水平表达，是静息免疫系统中LFA - 1的主要配体。ICAM - 3是一种信号转导分子，可能在启动免疫反应中起关键作用。对突变型ICAM - 3 Fc嵌合蛋白结合表达人LFA - 1的COS细胞的能力进行了定量分析。ICAM - 3上的LFA - 1结合位点位于N端的2个免疫球蛋白结构域。结构域3 - 5对黏附作用的贡献不显著。通过对结构域1和2中的14个点突变进行合理定位并结合模型研究，进一步解析了结合位点。在结构域1内，预测位于免疫球蛋白折叠的CC'FG面上的一簇残基（Glu37、Leu66、Ser68和Gln75）在LFA - 1结合中起主导作用。
