Intermediate monomer–dimer equilibrium structure of native ICAM-1: Implication for enhanced cell adhesion

• Published in: Experimental cell research 2011-01, Vol.317 (2), p.163-172
• Main Authors: Oh, Hyun-Mee, Kwon, Min-Sung, Kim, Hyang-Jin, Jeon, Byeong-Hun, Kim, Hye-Ran, Choi, Hyang-Ok, Na, Bo-Ra, Eom, Soo-Hyun, Song, Nam Woong, Jun, Chang-Duk
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Animals; Base Sequence; Cell adhesion; Cell adhesion & migration; Cell Adhesion - physiology; Cell Line; Cell Line, Transformed; Cercopithecus aethiops; CHO Cells; COS Cells; Cricetinae; Cricetulus; Dimer; Dimerization; DNA, Complementary; Endothelium, Vascular - cytology; Equilibrium; Humans; ICAM-1; Immunoglobulin superfamily; Intercellular Adhesion Molecule-1 - chemistry; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Intracellular domain; Jurkat Cells; Kidney - cytology; Macromolecular Substances - metabolism; Models, Structural; Molecular Sequence Data; Protein Structure, Tertiary - genetics; RNA, Small Interfering - metabolism; Transfection; Umbilical Veins - cytology
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2010.10.004

Dimeric intercellular adhesion molecule-1 (ICAM-1) has been known to more efficiently mediate cell adhesion than monomeric ICAM-1. Here, we found that truncation of the intracellular domain of ICAM-1 significantly enhances surface dimerization based on the two criteria: 1) the binding degree of monomer-specific antibody CA-7 and 2) the ratio of dimer/monomer when a mutation (L42 → C42) was introduced in the interface of domain 1. Mutation analysis revealed that the positively charged amino acids, including very membrane-proximal 505R, are essential for maintaining the structural transition between the monomer and dimer. Despite a strong dimer presentation, the ICAM-1 mutants lacking an intracellular domain (IC1ΔCTD) or containing R to A substitution in position 505 ( 505R/A) supported a lower degree of cell adhesion than did wild-type ICAM-1. Collectively, these results demonstrate that the native structure of surface ICAM-1 is not a dimer, but is an intermediate monomer–dimer equilibrium structure by which the effectiveness of ICAM-1 can be fully achieved.