Intermediate monomer-dimer equilibrium structure of native ICAM-1: implication for enhanced cell adhesion |
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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 |
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Affiliation: | aSchool of Life Sciences, and Immune Synapse Research Center, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea;bCenter for Nano-bio Convergence Research, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea |
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Abstract: | 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. |
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Keywords: | Abbreviations: ICAM-1, intercellular adhesion molecule-1 Ig, immunoglobulin LFA-1, lymphocyte function-associated antigen-1 GPI, glycosylphophatidylinositol SDF-1α, stromal-derived factor-1α FITC, fluorescein isothiocyanate |
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